{"_bicim": "stemmata-kutuphane", "surum": 3}
{"doi": "https://doi.org/10.1038/nbt1358", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2100772783"}
{"doi": "https://doi.org/10.1038/nbt.1990", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2086286404"}
{"doi": "https://doi.org/10.1038/nbt.2017", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2152265294"}
{"atif_sayisi": 2535, "atiflar": ["W111392919", "W1494491432", "W1520738779", "W1583256888", "W1597787921", "W1625702540", "W1873470920", "W1973454785", "W1974704457", "W1975359970", "W1976123775", "W1976686277", "W1982123744", "W1985640839", "W1986701803", "W1987642183", "W1988908019", "W1991738330", "W2006901566", "W2008340390", "W2011312875", "W2011588737", "W2015011627", "W2015787802", "W2016610889", "W2017338430", "W2021273781", "W2022816128", "W2022914311", "W2028672592", "W2031882612", "W2032295238", "W2035936653", "W2040473505", "W2042076664", "W2042916026", "W2043620856", "W2045268647", "W2052615604", "W2052750950", "W2054963713", "W2059384448", "W2060818930", "W2063013559", "W2063620211", "W2067381705", "W2067979493", "W2069232844", "W2072003755", "W2073206600", "W2073874786", "W2075204296", "W2075555703", "W2081046643", "W2082799841", "W2084612167", "W2086262311", "W2090895449", "W2093881154", "W2097981550", "W2100712519", "W2106293966", "W2107034836", "W2109467838", "W2112842133", "W2114869204", "W2115346062", "W2116247013", "W2118579211", "W2120281136", "W2122709827", "W2123885531", "W2128553601", "W2131174104", "W2132755748", "W2135129680", "W2135133228", "W2140132827", "W2140254301", "W2140765540", "W2143877481", "W2144785546", "W2146798821", "W2147012175", "W2147510335", "W2159664830", "W2159903725", "W2161182074", "W2165558270", "W2166393142", "W2301131921", "W2375169070", "W4205143742", "W4247904703"], "baslik": "The selectivity of protein kinase inhibitors: a further update", "doi": "https://doi.org/10.1042/bj20070797", "gerekce": "telifli görünüyor (lisans=`other-oa`, yayıncı=`Portland Press`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "other-oa", "yayinci": "Portland Press"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Mitogen-activated protein kinase kinase", "ASK1", "Cyclin-dependent kinase 9", "MAP kinase kinase kinase", "Biology", "Cyclin-dependent kinase 2", "Protein kinase B"], "kimlik": "W2046822015", "ozet": "The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes.", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Jenny Bain", "Lorna Plater", "Matt Elliott", "Natalia Shpiro", "C. James Hastie", "Hilary McLauchlan", "Iva Klevernic", "J. Simon C. Arthur", "Dario R. Alessi", "Philip Cohen"], "yil": 2007}
{"atif_sayisi": 2485, "atiflar": ["W3899755", "W33564209", "W189341708", "W283232088", "W1480178458", "W1502642972", "W1506674838", "W1507837421", "W1509419867", "W1511496806", "W1521493025", "W1568354597", "W1569096762", "W1578456230", "W1589866689", "W1595133660", "W1597175971", "W1603867644", "W1605748290", "W1620696626", "W1822167571", "W1852213635", "W1891400074", "W1914630957", "W1965858996", "W1969665533", "W1970078269", "W1971722347", "W1973454785", "W1974538311", "W1976115828", "W1978016402", "W1979416940", "W1980180619", "W1985174072", "W1992472345", "W1993282564", "W1999877090", "W2001692359", "W2005902831", "W2006404755", "W2007550845", "W2010944214", "W2015063877", "W2015223741", "W2015648136", "W2021062734", "W2023608322", "W2029770423", "W2034225514", "W2040752237", "W2044754653", "W2047453707", "W2050338578", "W2050829615", "W2051531396", "W2056682421", "W2059811943", "W2061574494", "W2064762154", "W2066799837", "W2068570002", "W2068669272", "W2068877244", "W2075473225", "W2079555764", "W2079876097", "W2082906412", "W2087376456", "W2100837269", "W2101141969", "W2103174300", "W2150086709", "W2151335002", "W2285120518", "W2320804891", "W2324512884", "W2401074096", "W2402016238", "W2404461233", "W2968059612"], "baslik": "The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C", "doi": "https://doi.org/10.1016/s0021-9258(18)98476-0", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Bisindolylmaleimide", "Protein kinase C", "Chemistry", "Protein kinase A", "Kinase", "Biochemistry", "Pharmacology"], "kimlik": "W1755902553", "ozet": "Staurosporine is the most potent inhibitor of protein kinase C (PKC) described in the literature with a half-maximal inhibitory concentration (IC50) of 10 nM. Nevertheless, this natural product is poorly selective when assayed against other protein kinases. In order to obtain specific PKC inhibitors, a series of bisindolylmaleimides has been synthesized. Structure-activity relationship studies allowed the determination of the substructure responsible for conferring high potency and lack of selectivity in the staurosporine molecule. Several aminoalkyl bisindolylmaleimides were found to be potent and selective PKC inhibitors (IC50 values from 5 to 70 nM). Among these compounds GF 109203X has been chosen for further studies aiming at the characterization of this chemical family. GF 109203X was a competitive inhibitor with respect to ATP (Ki = 14 +/- 3 NM) and displayed high selectivity for PKC as compared to five different protein kinases. We further determined the potency and specificity of GF 109203X in two cellular models: human platelets and Swiss 3T3 fibroblasts. GF 109203X efficiently prevented PKC-mediated phosphorylations of an Mr = 47,000 protein in platelets and of an Mr = 80,000 protein in Swiss 3T3 cells. In contrast, in the same models, the PKC inhibitor failed to prevent PKC-independent phosphorylations. GF 109203X inhibited collagen- and alpha-thrombin-induced platelet aggregation as well as collagen-triggered ATP secretion. However, ADP-dependent reversible aggregation was not modified. In Swiss 3T3 fibroblasts, GF 109203X reversed the inhibition of epidermal growth factor binding induced by phorbol 12,13-dibutyrate and prevented [3H] thymidine incorporation into DNA, only when this was elicited by growth promoting agents which activate PKC. Our results illustrate the potential of GF 109203X as a tool for studying the involvement of PKC in signal transduction pathways.", "tam_metin_adresi": "https://doi.org/10.1016/s0021-9258(18)98476-0", "yayinci": "Elsevier BV", "yazarlar": ["Dominique Toullec", "P. Pianetti", "Hervé Coste", "P. Bellevergue", "Thierry Grand‐Perret", "M. Ajakane", "V. Baudet", "P. Boissin", "Eric Boursier", "F. Loriolle"], "yil": 1991}
{"doi": "https://doi.org/10.1038/nm0596-561", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2016086822"}
{"atif_sayisi": 1959, "atiflar": ["W208730735", "W1513717105", "W1532405053", "W1561243612", "W1561731791", "W1562075782", "W1575040416", "W1575863011", "W1576212058", "W1583957430", "W1656644300", "W1817318311", "W1908892780", "W1922950570", "W1963569988", "W1975791322", "W1984754431", "W1993250562", "W2005411001", "W2009196480", "W2012071655", "W2018081460", "W2019300008", "W2025081899", "W2028669354", "W2035562653", "W2039132486", "W2045819374", "W2047945116", "W2048802942", "W2052561585", "W2055444005", "W2058839845", "W2064146442", "W2074416628", "W2074807562", "W2086245476", "W2088215519", "W2094126922", "W2110061443", "W2122048408", "W2123030732", "W2134352843", "W2134812217", "W2148426299", "W2168420719", "W2406970938", "W2409196608", "W4294216491"], "baslik": "Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor", "doi": "https://doi.org/10.1074/jbc.271.2.695", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Proto-oncogene tyrosine-protein kinase Src", "Tyrosine-kinase inhibitor", "Tyrosine kinase", "Tyrosine-protein kinase CSK", "Src family kinase", "Protein-Tyrosine Kinases", "Chemistry", "Tyrosine"], "kimlik": "W2090895449", "ozet": "Here, we have studied the activity of a novel protein-tyrosine kinase inhibitor that is selective for the Src family of tyrosine kinases. We have focused our study on the effects of this compound on T cell receptor-induced T cell activation, a process dependent on the activity of the Src kinases Lck and FynT. This compound is a nanomolar inhibitor of Lck and FynT, inhibits anti-CD3-induced protein-tyrosine kinase activity in T cells, demonstrates selectivity for Lck and FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation over non-T cell receptor-dependent phorbol 12-myristate 13-acetate/interleukin-2 (IL-2)-induced T cell proliferation. Interestingly, this compound selectively inhibits the induction of the IL-2 gene, but not the granulocyte-macrophage colony-stimulating factor or IL-2 receptor genes. This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the role of other Src family kinases in receptor function.", "tam_metin_adresi": "https://doi.org/10.1074/jbc.271.2.695", "yayinci": "Elsevier BV", "yazarlar": ["Jeffrey H. Hanke", "Joseph P. Gardner", "Robert L. Dow", "Paul S. Changelian", "William H. Brissette", "Elora J. Weringer", "Brian A. Pollok", "Patricia A. Connelly"], "yil": 1996}
{"atif_sayisi": 285, "atiflar": ["W1483308173", "W1572054273", "W1901732955", "W1916256274", "W2000590032", "W2002782759", "W2003334000", "W2014215007", "W2014330392", "W2022819740", "W2035320881", "W2038705787", "W2039433889", "W2042960115", "W2069302785", "W2091333494", "W2093804554", "W2109001944", "W2123414080", "W2135718475", "W2149447280", "W2153414586", "W2159659449", "W2159705610", "W2164858045", "W2295724055", "W2329371764", "W2416365354", "W2471841098", "W2525212149", "W2530335997", "W2533277983", "W2543549509", "W2559407770", "W2559743688", "W2562753811", "W2566103724", "W2584430503", "W2587810271", "W2588044396", "W2592397452", "W2607343491", "W2626892937", "W2744471826", "W2748091531", "W2749941863", "W2753412247", "W2759367587", "W2782539460", "W2782968698", "W2789471630", "W2807791746", "W2808333862", "W2950926826", "W4211144854", "W7074013758"], "baslik": "Clinical significance of Janus Kinase inhibitor selectivity", "doi": "https://doi.org/10.1093/rheumatology/key339", "gerekce": "açık lisans `cc-by` ticari TDM'e izin veriyor", "gerekce_kodu": "acik_lisans", "gerekce_param": {"lisans": "cc-by"}, "izin": "TAM", "kavramlar": ["Janus kinase", "Tyrosine kinase 2", "Tofacitinib", "Janus kinase 1", "Medicine", "Cytokine receptor", "Tyrosine kinase", "Janus kinase 2"], "kimlik": "W2903436036", "ozet": "Cytokines are key drivers of inflammation in RA, and anti-cytokine therapy has improved the outcome of RA. Janus Kinases (JAK) are intracellular tyrosine kinases linked to intracellular domains of many cytokine receptors. There are four JAK isoforms: JAK1, JAK2, JAK3 and TYK2. Different cytokine receptor families utilize specific JAK isoforms for signal transduction. Phosphorylation of JAK when cytokine binds to its cognate receptor leads to phosphorylation of other intracellular molecules that eventually leads to gene transcription. Oral JAK inhibitors (JAKi) have been developed as anti-cytokine therapy in RA. Two JAKi, tofacitinib and baricitinib, have been approved recently for the treatment of RA, and many JAKi are currently in development. JAKi inhibit JAK isoforms with different selectivity. This review discusses the efficacy and safety of JAKi in RA, in particular the potential clinical significance of JAKi selectivity.", "tam_metin_adresi": "https://academic.oup.com/rheumatology/article-pdf/58/6/953/28697447/key339.pdf", "yayinci": "Oxford University Press", "yazarlar": ["Ernest Choy"], "yil": 2018}
{"atif_sayisi": 1361, "atiflar": ["W31205294", "W145439482", "W1987013746", "W1987583691", "W2007420407", "W2030090912", "W2031882612", "W2045156702", "W2050535564", "W2054292493", "W2058743530", "W2060573548", "W2060632243", "W2080686146", "W2087555023", "W2124662474", "W2137705897", "W2139273584", "W2140292978", "W2140765540", "W2144785546", "W2150740687", "W2155305032", "W2161471780", "W2161614082", "W2163188200", "W2167039800", "W2170862003", "W6601296749"], "baslik": "Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity", "doi": "https://doi.org/10.1073/pnas.0711741105", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Cancer research", "V600E", "Biology", "Melanoma", "Cell cycle", "Apoptosis", "Mutation"], "kimlik": "W2154196978", "ozet": "BRAF(V600E) is the most frequent oncogenic protein kinase mutation known. Furthermore, inhibitors targeting \"active\" protein kinases have demonstrated significant utility in the therapeutic repertoire against cancer. Therefore, we pursued the development of specific kinase inhibitors targeting B-Raf, and the V600E allele in particular. By using a structure-guided discovery approach, a potent and selective inhibitor of active B-Raf has been discovered. PLX4720, a 7-azaindole derivative that inhibits B-Raf(V600E) with an IC(50) of 13 nM, defines a class of kinase inhibitor with marked selectivity in both biochemical and cellular assays. PLX4720 preferentially inhibits the active B-Raf(V600E) kinase compared with a broad spectrum of other kinases, and potent cytotoxic effects are also exclusive to cells bearing the V600E allele. Consistent with the high degree of selectivity, ERK phosphorylation is potently inhibited by PLX4720 in B-Raf(V600E)-bearing tumor cell lines but not in cells lacking oncogenic B-Raf. In melanoma models, PLX4720 induces cell cycle arrest and apoptosis exclusively in B-Raf(V600E)-positive cells. In B-Raf(V600E)-dependent tumor xenograft models, orally dosed PLX4720 causes significant tumor growth delays, including tumor regressions, without evidence of toxicity. The work described here represents the entire discovery process, from initial identification through structural and biological studies in animal models to a promising therapeutic for testing in cancer patients bearing B-Raf(V600E)-driven tumors.", "tam_metin_adresi": null, "yayinci": "National Academy of Sciences", "yazarlar": ["James Tsai", "John Tayu Lee", "Weiru Wang", "Jiazhong Zhang", "Hanna Cho", "Shumeye Mamo", "Ryan Bremer", "S. Gillette", "Jun Kong", "Nikolas K. Haass", "Katrin Sproesser", "Ling Li"], "yil": 2008}
{"atif_sayisi": 1863, "atiflar": ["W31811431", "W43617179", "W78645399", "W113835883", "W117181554", "W136692196", "W159822751", "W1484515711", "W1484647033", "W1486847030", "W1493025774", "W1511192707", "W1515935760", "W1516434930", "W1517887854", "W1523522784", "W1527859504", "W1543438374", "W1547508081", "W1561516029", "W1579308444", "W1784523242", "W1823191689", "W1862784902", "W1905017519", "W1950341920", "W1955338813", "W1964548815", "W1964785626", "W1964994147", "W1965737875", "W1968307241", "W1968452047", "W1970959706", "W1971915141", "W1972147469", "W1972832497", "W1976200310", "W1976462601", "W1982175258", "W1984368540", "W1984464853", "W1987322786", "W1988212011", "W1990037409", "W1990985056", "W1991150986", "W1993373381", "W1993712825", "W1994768909", "W1995040866", "W1995981655", "W1996668995", "W1999406799", "W1999884490", "W2000413883", "W2001097406", "W2002143632", "W2002321751", "W2002986019", "W2004241870", "W2005663928", "W2005702395", "W2009264307", "W2010895019", "W2011768933", "W2012040337", "W2012408120", "W2012750155", "W2016531738", "W2016934195", "W2017544644", "W2017627757", "W2017795530", "W2017873104", "W2018278847", "W2019494632", "W2019774786", "W2019889178", "W2020960046", "W2021284850", "W2021321634", "W2021730076", "W2022914311", "W2023108262", "W2023574496", "W2023591690", "W2024773308", "W2024829962", "W2025015037", "W2026542427", "W2028197171", "W2028724278", "W2030057932", "W2030148186", "W2030205108", "W2032731042", "W2034634754", "W2038725731", "W2038827434", "W2039099155", "W2039376197", "W2039400286", "W2039881470", "W2041183642", "W2041340494", "W2042524910", "W2042553090", "W2044728881", "W2047758068", "W2051958752", "W2052123857", "W2054065847", "W2054198559", "W2054266243", "W2054533694", "W2054541525", "W2054605326", "W2056945159", "W2057345518", "W2059069515", "W2059511698", "W2059603568", "W2061045914", "W2061061337", "W2062892961", "W2069416242", "W2070834812", "W2070924796", "W2071467777", "W2072190804", "W2072410510", "W2076309204", "W2076778684", "W2077053886", "W2079926187", "W2079950215", "W2080174833", "W2082776443", "W2084472730", "W2086286404", "W2086335000", "W2086758383", "W2087411946", "W2088434328", "W2088810018", "W2088970894", "W2090744742", "W2091818624", "W2092037329", "W2093369666", "W2093522627", "W2095144785", "W2096336546", "W2096996847", "W2097642975", "W2098101490", "W2098266773", "W2100124283", "W2100748836", "W2100772783", "W2103205445", "W2105192804", "W2107767441", "W2108349218", "W2108620810", "W2109306753", "W2110285722", "W2112319867", "W2113456155", "W2114215066", "W2116456927", "W2121300516", "W2122424184", "W2123695942", "W2124421822", "W2124681346", "W2124989653", "W2125048639", "W2129739698", "W2130248616", "W2131678991", "W2136016201", "W2136726091", "W2137005374", "W2139793053", "W2141091064", "W2144222210", "W2146139223", "W2146388445", "W2150913549", "W2152962086", "W2155023998", "W2158369873", "W2163017683", "W2164242115", "W2164437550", "W2165073006", "W2165122118", "W2166030259", "W2166594615", "W2169825456", "W2170444099", "W2170891294", "W2171271044", "W2171784256", "W2202150720", "W2339523901", "W2399249678", "W2410759048", "W2615170291", "W4256475235"], "baslik": "Skepinone-L, a Novel Potent and Highly Selective Inhibitor of p38 MAP Kinase, Effectively Impairs Platelet Activation and Thrombus Formation", "doi": "https://doi.org/10.1159/000350110", "gerekce": "açık lisans `cc-by` ticari TDM'e izin veriyor", "gerekce_kodu": "acik_lisans", "gerekce_param": {"lisans": "cc-by"}, "izin": "TAM", "kavramlar": ["p38 mitogen-activated protein kinases", "In vivo", "Kinase", "Mitogen-activated protein kinase", "Protein kinase A", "MAPK/ERK pathway", "Chemistry", "Pharmacology"], "kimlik": "W1988212011", "ozet": "BACKGROUND/AIMS: Platelets are critically important for primary haemostasis and the major players in thrombotic vascular occlusion. Platelets are activated by agonists, such as thrombin and collagen-related peptide as well as second-wave mediators including thromboxane A2 via different intracellular signaling pathways resulting in degranulation, aggregation and thrombus formation. Platelet activation is paralleled by phosphorylation and activation of p38 MAPK. The limited specificity of hitherto known p38 MAPK inhibitors precluded safe conclusions on the precise role of p38 MAPK in the regulation of platelet function. The present study examined the impact of Skepinone-L, a novel and highly selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), on platelet activation and thrombus formation. METHODS: Experiments were performed in freshly isolated human platelets. Protein phosphorylation was quantified by Western blotting, thromboxane B2 synthesis by enzyme immunoassay, ATP release by ChronoLume luciferin assay, cytosolic Ca(2+) concentration by Fura-2 fluorescence-measurements, platelet aggregation by a light transmissions measurement and in vitro thrombus formation by a flow chamber. RESULTS: Skepinone-L (1 μM) virtually abrogated the phosphorylation of platelet p38 MAPK substrate Hsp27 following stimulation with CRP (1 μg/ml), thrombin (5 mU/ml) or thromboxane A2 analogue U-46619 (1 μM). Furthermore, Skepinone-L significantly blunted activation-dependent platelet secretion and aggregation following threshold concentrations of CRP, thrombin and thromboxane A2 analogue U-46619. Skepinone-L did not impair platelet Ca(2+) signaling but prevented agonist-induced thromboxane A2 synthesis through abrogation of p38 MAPK-dependent phosphorylation of platelet cytosolic phospholipase A2 (cPLA2). Skepinone-L further markedly blunted thrombus formation under low (500-s) and high (1700-s) arterial shear rates. CONCLUSIONS: The present study discloses a powerful inhibiting effect of p38 MAPK-blocker Skepinone-L on platelet activation and thrombus formation.", "tam_metin_adresi": "https://www.karger.com/Article/Pdf/350110", "yayinci": "Karger Publishers", "yazarlar": ["Oliver Borst", "Britta Walker", "Patrick Münzer", "Antonella Russo", "Evi Schmid", "Caterina Faggio", "Boris Bigalke", "Stefan Laufer", "Meinrad Gawaz", "Florian Läng"], "yil": 2013}
{"doi": "https://doi.org/10.1016/j.chembiol.2005.04.011", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2117022661"}
{"doi": "https://doi.org/10.1038/nature08622", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2133963438"}
{"doi": "https://doi.org/10.1182/blood.v96.3.925", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2134094496"}
{"doi": "https://doi.org/10.1111/j.1432-1033.1997.t01-2-00527.x", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2135129680"}
{"doi": "https://doi.org/10.1007/978-1-61779-337-0_7", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Springer Science+Business Media` (P4310319900) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Springer Science+Business Media` (P4310319900) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2417500499"}
{"doi": "https://doi.org/10.1002/cmdc.200600221", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2019216438"}
{"atif_sayisi": 1419, "atiflar": ["W93433415", "W157488053", "W1981122694", "W1985389450", "W1988698939", "W1992534638", "W1995916005", "W1999463736", "W2003309405", "W2015616444", "W2019695814", "W2023553115", "W2024680115", "W2025215722", "W2034269086", "W2039771541", "W2043103956", "W2051349612", "W2055395862", "W2063329265", "W2064362422", "W2077945404", "W2084370215", "W2097255042", "W2098953839", "W2106123852", "W2108143474", "W2111369086", "W2119040192", "W2121664015", "W2122655800", "W2125211913", "W2131994307", "W2133958387", "W2137057588", "W2137084288", "W2138103542", "W2138798180", "W2140618607", "W2142739240", "W2147371405", "W2150081723", "W2153985422", "W2154626333", "W2224783441", "W2318605753", "W2409495547", "W3149591292", "W3153391969"], "baslik": "PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro", "doi": "https://doi.org/10.1186/bcr2419", "gerekce": "opt-out yayıncı `BioMed Central` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "BioMed Central"}, "izin": "TAM", "kavramlar": ["Surgical oncology", "Cancer research", "Estrogen receptor", "Breast cancer", "In vitro", "Cell growth", "Human breast", "Kinase"], "kimlik": "W2148345265", "ozet": "INTRODUCTION: Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines. METHODS: Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response. RESULTS: Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade. CONCLUSIONS: These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991", "tam_metin_adresi": "https://doi.org/10.1186/bcr2419", "yayinci": "BioMed Central", "yazarlar": ["Richard S. Finn", "Judy Dering", "Dylan Conklin", "Ondrej Kalous", "David J. Cohen", "Amrita Desai", "Charles Ginther", "Mohammad Atefi", "Isan Chen", "Camilla Fowst", "Gerret Los", "Dennis J. Slamon"], "yil": 2009}
{"doi": "https://doi.org/10.1038/nm1003", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2128553601"}
{"atif_sayisi": 4064, "atiflar": ["W80953942", "W111932728", "W884497578", "W1487207306", "W1494491432", "W1528756081", "W1583256888", "W1591210132", "W1597787921", "W1599213556", "W1601657500", "W1779286308", "W1908612571", "W1911507478", "W1921708445", "W1937671642", "W1969388212", "W1971915141", "W1973704051", "W1974353473", "W1976686277", "W1979993283", "W1985640839", "W1985888026", "W1986570146", "W1991738330", "W1998762942", "W2009445851", "W2011312875", "W2012051875", "W2015648136", "W2016610889", "W2022816128", "W2022914311", "W2030196438", "W2031882612", "W2032295238", "W2035221880", "W2035936653", "W2037894077", "W2043620856", "W2047980471", "W2063956233", "W2066607735", "W2067381705", "W2071775273", "W2073586734", "W2075204296", "W2082594472", "W2086262311", "W2093881154", "W2096950509", "W2105768236", "W2131162745", "W2166825418", "W2375169070"], "baslik": "Specificity and mechanism of action of some commonly used protein kinase inhibitors", "doi": "https://doi.org/10.1042/0264-6021:3510095", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Wortmannin", "Protein kinase A", "Chemistry", "c-Raf", "Protein kinase C", "Biochemistry", "Cyclin-dependent kinase 2"], "kimlik": "W2052750950", "ozet": "The specificities of 28 commercially available compounds reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases have been examined against a large panel of protein kinases. The compounds KT 5720, Rottlerin and quercetin were found to inhibit many protein kinases, sometimes much more potently than their presumed targets, and conclusions drawn from their use in cell-based experiments are likely to be erroneous. Ro 318220 and related bisindoylmaleimides, as well as H89, HA1077 and Y 27632, were more selective inhibitors, but still inhibited two or more protein kinases with similar potency. LY 294002 was found to inhibit casein kinase-2 with similar potency to phosphoinositide (phosphatidylinositol) 3-kinase. The compounds with the most impressive selectivity profiles were KN62, PD 98059, U0126, PD 184352, rapamycin, wortmannin, SB 203580 and SB 202190. U0126 and PD 184352, like PD 98059, were found to block the mitogen-activated protein kinase (MAPK) cascade in cell-based assays by preventing the activation of MAPK kinase (MKK1), and not by inhibiting MKK1 activity directly. Apart from rapamycin and PD 184352, even the most selective inhibitors affected at least one additional protein kinase. Our results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure. We propose guidelines for the use of protein kinase inhibitors in cell-based assays.", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Stephen Davies", "Helen Reddy", "Matilde Caivano", "Philip Cohen"], "yil": 2000}
{"atif_sayisi": 693, "atiflar": [], "baslik": "Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Wortmannin", "Phosphatidylinositol", "Kinase", "Chemistry", "Biochemistry", "Cell biology", "Biology"], "kimlik": "W1587932799", "ozet": "Phosphatidylinositol-3-kinase is an important enzyme for intracellular signaling. The microbial product wortmannin and some of its analogues have been shown to be potent inhibitors of phosphatidylinositol-3-kinase. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nM. Kinetic analysis demonstrates that wortmannin is a noncompetitive, irreversible inhibitor of phosphatidylinositol-3-kinase, with inactivation being both time- and concentration-dependent. Wortmannin has previously been reported to be an inhibitor of myosin light chain kinase but with an inhibitory concentration of 0.2 microM. Wortmannin was found not to be an inhibitor of phosphatidylinositol-4-kinase, protein kinase C, or protein tyrosine kinase. Wortmannin inhibited the formation of phosphatidylinositol-3-phosphates in intact cells. The results of the study suggest that wortmannin and its analogues may have utility as pharmacological probes for studying the actions of phosphatidylinositol-3-kinase.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Garth Powis", "Rosanne Bonjouklian", "Margareta Berggren", "Alfred Gallegos", "Robert T. Abraham", "Curtis L. Ashendel", "Leon H. Zalkow", "William F. Matter", "Jeffrey A. Dodge", "Gerald B. Grindey"], "yil": 1994}
{"doi": "https://doi.org/10.1016/s1074-5521(00)00025-9", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W1982958012"}
{"doi": "https://doi.org/10.1016/0014-5793(89)81494-2", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2015648136"}
{"doi": "https://doi.org/10.1182/blood.v90.9.3691", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W120676909"}
{"doi": "https://doi.org/10.1016/j.cub.2006.12.037", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2029108033"}
{"doi": "https://doi.org/10.1038/358070a0", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2024839583"}
{"atif_sayisi": 532, "atiflar": ["W261722493", "W1487365829", "W1547974121", "W1550017207", "W1568928604", "W1592772777", "W1639404500", "W1985395951", "W2015571904", "W2015648136", "W2020059934", "W2027355347", "W2074002103", "W2075898803", "W2078133735", "W2086524338", "W2091673674", "W2136674751", "W2142248261", "W2384401244", "W4211131955", "W4244667180", "W6609200041"], "baslik": "Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C", "doi": "https://doi.org/10.1042/bj2940335", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Protein kinase C", "Staurosporine", "Isozyme", "PKC alpha", "Selectivity", "Signal transduction", "Chemistry", "Alpha (finance)"], "kimlik": "W1822066871", "ozet": "The protein kinase C (PKC) family of isoenzymes is believed to mediate a wide range of signal-transduction pathways in many different cell types. A series of bisindolylmaleimides have been evaluated as inhibitors of members of the conventional PKC family (PKCs-alpha, -beta, -gamma) and of a representative of the new, Ca(2+)-independent, PKC family, PKC-epsilon. In contrast with the indolocarbazole staurosporine, all the bisindolylmaleimides investigated showed slight selectivity for PKC-alpha over the other isoenzymes examined. In addition, bisindolylmaleimides bearing a conformationally restricted side-chain were less active as inhibitors of PKC-epsilon. Most noticeable of these was Ro 32-0432, which showed a 10-fold selectivity for PKC-alpha and a 4-fold selectivity for PKC-beta I over PKC-epsilon.", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Sandra E. Wilkinson", "Peter J. Parker", "John Nixon"], "yil": 1993}
{"atif_sayisi": 513, "atiflar": ["W1982114584", "W1988908019", "W2004922458", "W2016086822", "W2019293169", "W2022658303", "W2030205108", "W2042439588", "W2045401053", "W2062366098", "W2063897912", "W2066469176", "W2085562786", "W2088806906", "W2116398087", "W2119694628", "W2123759975", "W2134399756", "W2140490890", "W2151504205", "W4230663824"], "baslik": "Structural Bioinformatics-Based Design of Selective, Irreversible Kinase Inhibitors", "doi": "https://doi.org/10.1126/science1108367", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Selectivity", "Cysteine", "Threonine", "Biochemistry", "Protein kinase A", "Active site", "Chemistry"], "kimlik": "W2114869204", "ozet": "The active sites of 491 human protein kinase domains are highly conserved, which makes the design of selective inhibitors a formidable challenge. We used a structural bioinformatics approach to identify two selectivity filters, a threonine and a cysteine, at defined positions in the active site of p90 ribosomal protein S6 kinase (RSK). A fluoromethylketone inhibitor, designed to exploit both selectivity filters, potently and selectively inactivated RSK1 and RSK2 in mammalian cells. Kinases with only one selectivity filter were resistant to the inhibitor, yet they became sensitized after genetic introduction of the second selectivity filter. Thus, two amino acids that distinguish RSK from other protein kinases are sufficient to confer inhibitor sensitivity.", "tam_metin_adresi": null, "yayinci": "American Association for the Advancement of Science", "yazarlar": ["Michael S. Cohen", "Chao Zhang", "Kevan M. Shokat", "Jack Taunton"], "yil": 2005}
{"doi": "https://doi.org/10.1016/s0969-2126(98)00113-0", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2097066538"}
{"atif_sayisi": 1040, "atiflar": ["W219550331", "W233869125", "W284870166", "W1495712810", "W1532019756", "W1559714867", "W1586129343", "W1603098046", "W1611565221", "W1679229092", "W1770702054", "W1784095256", "W1795179533", "W1837651204", "W1903437307", "W1937671642", "W1953884850", "W1969328947", "W1969855058", "W1986469266", "W1986559037", "W1986758971", "W1987644022", "W1992388470", "W1994360534", "W2003598961", "W2009240587", "W2018442334", "W2019931546", "W2023453327", "W2043850275", "W2045247659", "W2046516822", "W2048185125", "W2049972026", "W2050358495", "W2050740674", "W2053375897", "W2054979979", "W2056242981", "W2069637592", "W2076820945", "W2093498435", "W2095140485", "W2100285612", "W2105053096", "W2109689528", "W2111080918", "W2114098415", "W2144383844", "W2232660545", "W2612961129"], "baslik": "SU5416 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Vascular endothelial growth inhibitor", "Vascular endothelial growth factor", "Cancer research", "Receptor tyrosine kinase", "Tyrosine kinase", "Vascular endothelial growth factor B", "Biology", "Tyrosine-kinase inhibitor"], "kimlik": "W2166825418", "ozet": "SU5416, a novel synthetic compound, is a potent and selective inhibitor of the Flk-1/KDR receptor tyrosine kinase that is presently under evaluation in Phase I clinical studies for the treatment of human cancers. SU5416 was shown to inhibit vascular endothelial growth factor-dependent mitogenesis of human endothelial cells without inhibiting the growth of a variety of tumor cells in vitro. In contrast, systemic administration of SU5416 at nontoxic doses in mice resulted in inhibition of subcutaneous tumor growth of cells derived from various tissue origins. The antitumor effect of SU5416 was accompanied by the appearance of pale white tumors that were resected from drug-treated animals, supporting the antiangiogenic property of this agent. These findings support that pharmacological inhibition of the enzymatic activity of the vascular endothelial growth factor receptor represents a novel strategy for limiting the growth of a wide variety of tumor types.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["T. Annie T. Fong", "Laura K. Shawver", "Li Sun", "Cho Tang", "H. App", "Thomas Powell", "Y. H. Kim", "Randall Schreck", "Xueyan Wang", "Werner Risau", "A. Ullrich", "K. Peter Hirth"], "yil": 1999}
{"doi": "https://doi.org/10.1182/blood-2010-03-275305", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2027971058"}
{"atif_sayisi": 3041, "atiflar": ["W591968967", "W1020831558", "W1505475872", "W1516476750", "W1572416479", "W1573821584", "W1575281088", "W1607023443", "W1823225325", "W1848358197", "W1854733189", "W1870773788", "W1900380445", "W1964504843", "W1968672667", "W1971915141", "W1974389559", "W1983729225", "W1988409513", "W1993963200", "W2001521752", "W2024942502", "W2035936653", "W2045074115", "W2047182549", "W2047263793", "W2074362036", "W2076086359", "W2083422438", "W2088927230", "W2089343995", "W2103382643", "W2107020701", "W2125566475", "W2126836839", "W2132188426", "W2144033050", "W2155189322", "W2159390753", "W2162491741", "W2175322775", "W2328830747", "W2332513609", "W2399249678", "W2410952672", "W4302590117"], "baslik": "Identification of a Novel Inhibitor of Mitogen-activated Protein Kinase Kinase", "doi": "https://doi.org/10.1074/jbc.273.29.18623", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["MEK inhibitor", "MAPK/ERK pathway", "Protein kinase A", "Mitogen-activated protein kinase kinase", "Kinase", "Transactivation", "Chemistry", "MAP kinase kinase kinase"], "kimlik": "W2086262311", "ozet": "The compound U0126 (1,4-diamino-2,3-dicyano-1, 4-bis[2-aminophenylthio]butadiene) was identified as an inhibitor of AP-1 transactivation in a cell-based reporter assay. U0126 was also shown to inhibit endogenous promoters containing AP-1 response elements but did not affect genes lacking an AP-1 response element in their promoters. These effects of U0126 result from direct inhibition of the mitogen-activated protein kinase kinase family members, MEK-1 and MEK-2. Inhibition is selective for MEK-1 and -2, as U0126 shows little, if any, effect on the kinase activities of protein kinase C, Abl, Raf, MEKK, ERK, JNK, MKK-3, MKK-4/SEK, MKK-6, Cdk2, or Cdk4. Comparative kinetic analysis of U0126 and the MEK inhibitor PD098059 (Dudley, D. T., Pang, L., Decker, S. J., Bridges, A. J., and Saltiel, A. R. (1995) Proc. Natl. Acad. Sci U. S. A. 92, 7686-7689) demonstrates that U0126 and PD098059 are noncompetitive inhibitors with respect to both MEK substrates, ATP and ERK. We further demonstrate that the two compounds bind to deltaN3-S218E/S222D MEK in a mutually exclusive fashion, suggesting that they may share a common or overlapping binding site(s). Quantitative evaluation of the steady state kinetics of MEK inhibition by these compounds reveals that U0126 has approximately 100-fold higher affinity for deltaN3-S218E/S222D MEK than does PD098059. We further tested the effects of these compounds on the activity of wild type MEK isolated after activation from stimulated cells. Surprisingly, we observe a significant diminution in affinity of both compounds for wild type MEK as compared with the deltaN3-S218E/S222D mutant enzyme. These results suggest that the affinity of both compounds is mediated by subtle conformational differences between the two activated MEK forms. The MEK affinity of U0126, its selectivity for MEK over other kinases, and its cellular efficacy suggest that this compound will serve as a powerful tool for in vitro and cellular investigations of mitogen-activated protein kinase-mediated signal transduction.", "tam_metin_adresi": "https://doi.org/10.1074/jbc.273.29.18623", "yayinci": "Elsevier BV", "yazarlar": ["Margaret Favata", "Kurumi Y. Horiuchi", "Elizabeth J. Manos", "Andrea J. Daulerio", "Deborah A. Stradley", "Wendi S. Feeser", "Drew E. Van Dyk", "William J. Pitts", "Richard A. Earl", "Frank W. Hobbs", "Robert A. Copeland", "Ronald L. Magolda"], "yil": 1998}
{"doi": "https://doi.org/10.1038/nchembio.538", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2124681346"}
{"atif_sayisi": 513, "atiflar": ["W1597787921", "W1631908837", "W1639582946", "W1875580551", "W1956617330", "W1970197743", "W1971140803", "W1972343960", "W1974003788", "W1975386736", "W1976195995", "W1978639260", "W1978929059", "W1984160018", "W1984226397", "W1986240377", "W1989013915", "W1992388470", "W1992509138", "W1992878563", "W1992945955", "W1993860023", "W1998700502", "W2002207761", "W2003706451", "W2005904989", "W2011588737", "W2012334764", "W2013928497", "W2015636345", "W2015786768", "W2016086822", "W2018390794", "W2019619408", "W2021497478", "W2024680115", "W2030205108", "W2033989981", "W2037015930", "W2038009022", "W2039478311", "W2040736465", "W2043696829", "W2048769310", "W2048814899", "W2049507332", "W2049830830", "W2050422354", "W2050537958", "W2052221882", "W2055536399", "W2058658881", "W2059347064", "W2062120857", "W2062366098", "W2065289702", "W2066123607", "W2067455153", "W2067754613", "W2069506489", "W2088806906", "W2089528428", "W2091455173", "W2093423704", "W2096286606", "W2099938880", "W2103293485", "W2110304343", "W2110818745", "W2113662093", "W2113788015", "W2114654929", "W2115363065", "W2115427263", "W2117022661", "W2118460316", "W2119392004", "W2121895929", "W2124848654", "W2128553601", "W2129707387", "W2131174104", "W2132670577", "W2133051701", "W2134207765", "W2135732933", "W2137429755", "W2138778824", "W2140557275", "W2140760855", "W2141743775", "W2142109435", "W2142820798", "W2147156144", "W2148763134", "W2150703483", "W2156578605", "W2156972915", "W2157153074", "W2158722505", "W2160053097", "W2161835431", "W2166344128", "W2166393142", "W2248972813", "W2548392785", "W2914443241", "W2949985550", "W3049347071", "W4247904703", "W4295216797"], "baslik": "Molecular Recognition of Protein Kinase Binding Pockets for Design of Potent and Selective Kinase Inhibitors", "doi": "https://doi.org/10.1021/jm0608107", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Chemical Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Chemical Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Citation", "Kinase", "Icon", "Computer science", "Information retrieval", "Library science", "World Wide Web", "Chemistry"], "kimlik": "W2049885874", "ozet": "ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTMolecular Recognition of Protein Kinase Binding Pockets for Design of Potent and Selective Kinase InhibitorsJeffrey Jie-Lou LiaoView Author Information TransTech Pharma, 4170 Mendenhall Oaks Parkway, High Point, North Carolina 27265, and Department of Chemistry, Duke University, Durham, North Carolina 27708 Cite this: J. Med. Chem. 2007, 50, 3, 409–424Publication Date (Web):January 10, 2007Publication History Received10 July 2006Published online10 January 2007Published inissue 8 February 2007https://pubs.acs.org/doi/10.1021/jm0608107https://doi.org/10.1021/jm0608107review-articleACS PublicationsCopyright © 2007 American Chemical SocietyRequest reuse permissionsArticle Views9361Altmetric-Citations417LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Adenine,Conformation,Inhibitors,Monomers,Peptides and proteins Get e-Alerts", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Jie-Lou Liao"], "yil": 2007}
{"atif_sayisi": 512, "atiflar": ["W1545201063", "W1566185742", "W1911118961", "W1974376665", "W1976214441", "W1978522011", "W1978985435", "W1985075123", "W1992708996", "W1993054739", "W1998600720", "W1999319877", "W2005766257", "W2007305884", "W2007618242", "W2011588737", "W2014613601", "W2015636345", "W2021606592", "W2027427219", "W2036804890", "W2037652830", "W2039771541", "W2045753932", "W2046767660", "W2049830830", "W2058513001", "W2064850712", "W2065447262", "W2066360911", "W2072906848", "W2080443370", "W2089528428", "W2090377897", "W2113604152", "W2117263757", "W2117650991", "W2132229312", "W2135129680", "W2138577306", "W2143365610", "W2143805046", "W2147691086", "W2154046401", "W2166317851", "W2174174865", "W2176395098", "W2176977927", "W2915288695", "W2949985550"], "baslik": "Discovery of a Potent and Selective Inhibitor of Cyclin-Dependent Kinase 4/6", "doi": "https://doi.org/10.1021/jm049354h", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Cyclin-dependent kinase", "Chemistry", "Kinase", "Selectivity", "Small molecule", "In vitro", "Pharmacology", "Structure–activity relationship"], "kimlik": "W1985389450", "ozet": "A pharmacological approach to inhibition of cyclin-dependent kinases 4 and 6 (Cdk4/6) using highly selective small molecule inhibitors has the potential to provide novel cancer therapies for clinical use. Achieving high levels of selectivity for Cdk4/6, versus other ATP-dependent kinases, presents a significant challenge. The pyrido[2,3-d]pyrimidin-7-one template provides an effective platform for the inhibition of a broad cross-section of kinases, including Cdks. It is now demonstrated that the modification of pyrido[2,3-d]pyrimidin-7-ones to include a 2-aminopyridine side chain at the C2-position provides inhibitors with exquisite selectivity for Cdk4/6 in vitro. This selectivity profile is recapitulated in cells where the most selective inhibitors create a G(1) block at concentrations up to 100-fold the IC(50) for cell proliferation. On the basis of its selectivity profile and pharmacokinetic profile, compound 43 (PD 0332991) was identified as a drug candidate for the treatment of cancer.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Peter L. Toogood", "Patricia J. Harvey", "Joseph T. Repine", "Derek Sheehan", "Scott N. VanderWel", "Hairong Zhou", "Paul R. Keller", "Dennis J. McNamara", "Debra Sherry", "Tong Zhu", "Joanne Brodfuehrer", "Chung Sik Choi"], "yil": 2005}
{"atif_sayisi": 3146, "atiflar": [], "baslik": "Specificity and mechanism of action of some commonly used protein kinase inhibitors", "doi": "https://doi.org/10.1042/bj3510095", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`Portland Press`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "Portland Press"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Wortmannin", "Protein kinase A", "Chemistry", "c-Raf", "Biochemistry", "Protein kinase C", "Cyclin-dependent kinase 2"], "kimlik": "W4247904703", "ozet": "The specificities of 28 commercially available compounds reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases have been examined against a large panel of protein kinases. The compounds KT 5720, Rottlerin and quercetin were found to inhibit many protein kinases, sometimes much more potently than their presumed targets, and conclusions drawn from their use in cell-based experiments are likely to be erroneous. Ro 318220 and related bisindoylmaleimides, as well as H89, HA1077 and Y 27632, were more selective inhibitors, but still inhibited two or more protein kinases with similar potency. LY 294002 was found to inhibit casein kinase-2 with similar potency to phosphoinositide (phosphatidylinositol) 3-kinase. The compounds with the most impressive selectivity profiles were KN62, PD 98059, U0126, PD 184352, rapamycin, wortmannin, SB 203580 and SB 202190. U0126 and PD 184352, like PD 98059, were found to block the mitogen-activated protein kinase (MAPK) cascade in cell-based assays by preventing the activation of MAPK kinase (MKK1), and not by inhibiting MKK1 activity directly. Apart from rapamycin and PD 184352, even the most selective inhibitors affected at least one additional protein kinase. Our results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure. We propose guidelines for the use of protein kinase inhibitors in cell-based assays.", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Stephen Davies", "Helen Reddy", "Matilde Caivano", "Philip Cohen"], "yil": 2000}
{"doi": "https://doi.org/10.1038/nrc2559", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2077804275"}
{"doi": "https://doi.org/10.1128/mcb.20.23.9018-9027.2000", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Taylor & Francis` (P4310320547) `Informa` grubuna ait: Taylor & Francis ana şirketi · 157K eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Taylor & Francis` (P4310320547) `Informa` grubuna ait: Taylor & Francis ana şirketi · 157K eser"}, "izin": "ENGELLI", "kimlik": "W2132755748"}
{"atif_sayisi": 212, "atiflar": ["W125106425", "W1495668897", "W1964230131", "W1964321121", "W1979563875", "W2004026035", "W2043103956", "W2045156702", "W2089288294", "W2089973951", "W2095156669", "W2097449310", "W2097988373", "W2108182027", "W2110444464", "W2111039168", "W2115351494", "W2123206362", "W2125730396", "W2130841637", "W2136701318", "W2136752280", "W2141393790", "W2145477245", "W2147340476", "W2160067245", "W2163755494", "W2166291746", "W2169560977", "W2184278156", "W2245002095", "W2280407369", "W3089528479", "W4240479615", "W4248204656", "W6629773897", "W6686023826"], "baslik": "Lapatinib, a Dual EGFR and HER2 Kinase Inhibitor, Selectively Inhibits HER2-Amplified Human Gastric Cancer Cells and is Synergistic with Trastuzumab In vitro and In vivo", "doi": "https://doi.org/10.1158/1078-0432.ccr-09-1112", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Lapatinib", "Trastuzumab", "Erlotinib", "Medicine", "Pharmacology", "Cancer research", "In vivo", "Cancer"], "kimlik": "W2147551134", "ozet": "PURPOSE: HER2 amplification occurs in 18% to 27% of gastric and gastroesophageal junction cancers. Lapatinib, a potent ATP-competitive inhibitor simultaneously inhibits both EGFR and HER2. To explore the role of HER family biology in upper gastrointestinal cancers, we evaluated the effect of lapatinib, erlotinib, and trastuzumab in a panel of molecularly characterized human upper gastrointestinal cancer cell lines and xenografts. EXPERIMENTAL DESIGN: EGFR and HER2 protein expression were determined in a panel of 14 human upper gastrointestinal cancer cell lines and HER2 status was assessed by fluorescent in situ hybridization. Dose-response curves were generated to determine sensitivity to lapatinib, erlotinib, and trastuzumab. In HER2-amplified cells, the combination of trastuzumab and lapatinib was evaluated using the median effects principal. The efficacy of lapatinib, trastuzumab, or the combination was examined in HER2-amplified xenograft models. RESULTS: Lapatinib had concentration-dependent antiproliferative activity across the panel with the greatest effects in HER2-amplified cells. There was no association between EGFR protein expression and sensitivity to any of the HER-targeted agents. Cell cycle analysis revealed that lapatinib induced G(1) arrest in sensitive lines and phosphorylated AKT and phosphorylated ERK were decreased in response to lapatinib as well. The combination of lapatinib and trastuzumab was highly synergistic in inhibiting cell growth with a combination index of <1. The combination also induced greater decreases in AKT and ERK activation, G(0)-G(1) cell cycle arrest, and increased rates of apoptosis. In vivo studies showed that the combination of lapatinib and trastuzumab had greater antitumor efficacy than either drug alone. CONCLUSION: Together, these data suggest that lapatinib has activity in HER2-amplified upper gastrointestinal cancer and supports the ongoing clinical investigation of lapatinib in patients with HER2-amplified disease.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Zev A. Wainberg", "Adrian Anghel", "Amrita Desai", "Raul Ayala", "Tong Luo", "Brent Safran", "Marlena S. Fejzo", "J. Randolph Hecht", "Dennis J. Slamon", "Richard S. Finn"], "yil": 2010}
{"atif_sayisi": 1502, "atiflar": ["W49411393", "W948493078", "W974097272", "W1498131948", "W1503152793", "W1576399086", "W1583504083", "W1599213556", "W1661233179", "W1775749144", "W1970587959", "W1973454785", "W1978349791", "W1982477399", "W1985849715", "W1989425013", "W1992623778", "W1994231412", "W2028598564", "W2041951812", "W2062850394", "W2081386962", "W2088818868", "W2123698545", "W2158028807", "W2160235865", "W2183970233", "W2440125231", "W3105898142"], "baslik": "Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.", "doi": "https://doi.org/10.1016/s0021-9258(19)34116-x", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Forskolin", "Protein kinase A", "Neurite", "Phosphorylation", "Chemistry", "Protein kinase inhibitor", "Cell biology", "Molecular biology"], "kimlik": "W1481438484", "ozet": "A newly synthesized isoquinolinesulfonamide, H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide), was shown to have a potent and selective inhibitory action against cyclic AMP-dependent protein kinase (protein kinase A), with an inhibition constant of 0.048 +/- 0.008 microM. H-89 exhibited weak inhibitory action against other kinases and Ki values of the compound for these kinases, including cGMP-dependent protein kinase (protein kinase G), Ca2+/phospholipid-dependent protein kinase (protein kinase C), casein kinase I and II, myosin light chain kinase, and Ca2+/calmodulin-dependent protein kinase II were 0.48 +/- 0.13, 31.7 +/- 15.9, 38.3 +/- 6.0, 136.7 +/- 17.0, 28.3 +/- 17.5, and 29.7 +/- 8.1 microM, respectively. Kinetic analysis indicated that H-89 inhibits protein kinase A, in competitive fashion against ATP. To examine the role of protein kinase A in neurite outgrowth of PC12 cells, H-89 was applied along with nerve growth factor (NGF), forskolin, or dibutyryl cAMP. Pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, and the NGF-induced protein phosphorylation was not not inhibited. H-89 also significantly inhibited the forskolin-induced neurite outgrowth from PC12D cells. This inhibition also occurred when H-89 was added before the addition of dibutyryl cAMP. Pretreatment of PC12D cells with H-89 (30 microM) inhibited significantly cAMP-dependent histone IIb phosphorylation activity in cell lysates but did not affect other protein phosphorylation activity such as cGMP-dependent histone IIb phosphorylation activity, Ca2+/phospholipid-dependent histone IIIs phosphorylation activity, Ca2+/calmodulin-dependent myosin light chain phosphorylation activity, and alpha-casein phosphorylation activity. However, this protein kinase A inhibitor did not inhibit the NGF-induced neurite outgrowth from PC12D cells. Thus, the forskolin- and dibutyryl cAMP-induced neurite outgrowth is apparently mediated by protein kinase A while the NGF-induced neurite outgrowth is mediated by a protein kinase A-independent pathway.", "tam_metin_adresi": "https://doi.org/10.1016/s0021-9258(19)34116-x", "yayinci": "Elsevier BV", "yazarlar": ["Takashi Chijiwa", "Akihiko Mishima", "Masatoshi Hagiwara", "Mamoru Sano", "Kensuke Hayashi", "Tomoyuki Inoue", "K. Naito", "T. TOSHIOKA", "Hisashi Hidaka"], "yil": 1990}
{"atif_sayisi": 586, "atiflar": ["W1494491432", "W1500667430", "W1639582946", "W1966699920", "W1973259070", "W1995216176", "W1996160829", "W2000896073", "W2003349514", "W2010890298", "W2014252192", "W2022524230", "W2031111848", "W2034470191", "W2036614475", "W2042834671", "W2046352484", "W2050422354", "W2056027221", "W2072667421", "W2074854146", "W2079822637", "W2080686146", "W2117852040", "W2122051507", "W2124662474", "W2129429534", "W2156509877", "W2159594827", "W2163188200", "W2163295338", "W2246411714", "W2273990438", "W6683827157"], "baslik": "Biological Characterization of ARRY-142886 (AZD6244), a Potent, Highly Selective Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor", "doi": "https://doi.org/10.1158/1078-0432.ccr-06-1150", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "MAPK/ERK pathway", "Protein kinase A", "Cell growth", "Mitogen-activated protein kinase kinase", "Phosphorylation", "Biology", "Cancer research"], "kimlik": "W2157016650", "ozet": "PURPOSE: The Ras-Raf-mitogen-activated protein kinase kinase (MEK) pathway is overactive in many human cancers and is thus a target for novel therapeutics. We have developed a highly potent and selective inhibitor of MEK1/2. The purpose of these studies has been to show the biological efficacy of ARRY-142886 (AZD6244) in enzymatic, cellular, and animal models. EXPERIMENTAL DESIGN: The ability of ARRY-142886 to inhibit purified MEK1 as well as other kinases was evaluated. Its effects on extracellular signal-regulated kinase (ERK) phosphorylation and proliferation in several cell lines were also determined. Finally, the inhibitor was tested in HT-29 (colorectal) and BxPC3 (pancreatic) xenograft tumor models. RESULTS: The IC(50) of ARRY-142886 was determined to be 14 nmol/L against purified MEK1. This activity is not competitive with ATP, which is consistent with the high specificity of compound for MEK1/2. Basal and epidermal growth factor-induced ERK1/2 phosphorylation was inhibited in several cell lines as well as 12-O-tetradecanoylphorbol-13-acetate-induced ERK1/2 phosphorylation in isolated peripheral blood mononuclear cells. Treatment with ARRY-142886 resulted in the growth inhibition of several cell lines containing B-Raf and Ras mutations but had no effect on a normal fibroblast cell line. When dosed orally, ARRY-142886 was capable of inhibiting both ERK1/2 phosphorylation and growth of HT-29 xenograft tumors in nude mice. Tumor regressions were also seen in a BxPC3 xenograft model. In addition, tumors remained responsive to growth inhibition after a 7-day dosing holiday. CONCLUSIONS: ARRY-142886 is a potent and selective MEK1/2 inhibitor that is highly active in both in vitro and in vivo tumor models. This compound is currently being investigated in clinical studies.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Tammie C. Yeh", "Vivienne Marsh", "Bryan A. Bernat", "Josh Ballard", "Heidi Colwell", "R J Evans", "Janet Parry", "Darin Smith", "Barbara J. Brandhuber", "Stefan Groß", "Allison Marlow", "Brian Hurley"], "yil": 2007}
{"atif_sayisi": 800, "atiflar": ["W1789901929", "W1980102456", "W1983698019", "W1995197723", "W1999999605", "W2000731858", "W2005496215", "W2018938558", "W2021012077", "W2033810893", "W2035521247", "W2052746044", "W2061196778", "W2073898739", "W2078434966", "W2080100938", "W2086524655", "W2088254174", "W2089119460", "W2093529069", "W2094817491", "W2098912234", "W2101988823", "W2102148658", "W2102891343", "W2104381422", "W2107614388", "W2113432343", "W2116622644", "W2117028091", "W2123996523", "W2126783165", "W2136676465", "W2137261869", "W2158111020", "W2158305336", "W4238567307", "W6638342167"], "baslik": "AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity", "doi": "https://doi.org/10.1158/0008-5472.can-09-1751", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["mTORC1", "PI3K/AKT/mTOR pathway", "mTORC2", "Protein kinase B", "Kinase", "Cell growth", "Mechanistic target of rapamycin", "Phosphorylation"], "kimlik": "W2154836325", "ozet": "The mammalian target of rapamycin (mTOR) kinase forms two multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, cell survival, and autophagy. Allosteric inhibitors of mTORC1, such as rapamycin, have been extensively used to study tumor cell growth, proliferation, and autophagy but have shown only limited clinical utility. Here, we describe AZD8055, a novel ATP-competitive inhibitor of mTOR kinase activity, with an IC50 of 0.8 nmol/L. AZD8055 showed excellent selectivity (approximately 1,000-fold) against all class I phosphatidylinositol 3-kinase (PI3K) isoforms and other members of the PI3K-like kinase family. Furthermore, there was no significant activity against a panel of 260 kinases at concentrations up to 10 micromol/L. AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. In vitro, AZD8055 potently inhibits proliferation and induces autophagy in H838 and A549 cells. In vivo, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT at plasma concentrations leading to tumor growth inhibition. Notably, AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human tumor types. AZD8055 is currently in phase I clinical trials.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Christine M. Chresta", "Barry R. Davies", "Ian Hickson", "Tom Harding", "Sabina Cosulich", "Susan E. Critchlow", "John P. Vincent", "Rebecca Ellston", "Darren Jones", "Patrizia Sini", "Dominic I. James", "Zoë Howard"], "yil": 2009}
{"atif_sayisi": 418, "atiflar": ["W101749175", "W1490860457", "W1552274890", "W1592402132", "W1972148009", "W1974903851", "W1992541155", "W1998990808", "W2012952884", "W2013041762", "W2016518678", "W2023977554", "W2024324841", "W2034004457", "W2041415161", "W2050509360", "W2050596106", "W2051515492", "W2053314612", "W2053690380", "W2073283646", "W2083612980", "W2094473234", "W2095226581", "W2102050170", "W2123334268", "W2131557977", "W2137601120", "W2140765540", "W2161282346", "W2162658917", "W2171405465", "W2274675847", "W2281555888", "W3141504478", "W3146462826", "W4230756767", "W4406766238"], "baslik": "Masitinib (AB1010), a Potent and Selective Tyrosine Kinase Inhibitor Targeting KIT", "doi": "https://doi.org/10.1371/journal.pone.0007258", "gerekce": "açık lisans `cc-by` ticari TDM'e izin veriyor", "gerekce_kodu": "acik_lisans", "gerekce_param": {"lisans": "cc-by"}, "izin": "TAM", "kavramlar": ["Tyrosine-kinase inhibitor", "Tyrosine kinase", "Cancer research", "Stem cell factor", "Imatinib", "Biology", "Pharmacology"], "kimlik": "W2106986615", "ozet": "BACKGROUND: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010), a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. METHODOLOGY/PRINCIPAL FINDINGS: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC(50)) of 200+/-40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC(50) of 150+/-80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. CONCLUSIONS: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity.", "tam_metin_adresi": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0007258&type=printable", "yayinci": "Public Library of Science", "yazarlar": ["Patrice Dubreuil", "Sébastien Letard", "Marco A. Ciufolini", "Laurent Gros", "Martine Humbert", "Nathalie Castéran", "Laurence Borge", "Bérengère Hajem", "Anne Lermet", "Wolfgang Sippl", "Edwige Voisset", "Michel Arock"], "yil": 2009}
{"doi": "https://doi.org/10.1016/s1535-6108(04)00051-0", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Cell Press` (P4310315673) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Cell Press` (P4310315673) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W1999030960"}
{"doi": "https://doi.org/10.1007/s12154-009-0023-9", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Springer Science+Business Media` (P4310319900) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Springer Science+Business Media` (P4310319900) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W1998071315"}
{"atif_sayisi": 929, "atiflar": ["W1426393029", "W1522491463", "W1542053886", "W1557061959", "W1567292196", "W1966843521", "W1969914656", "W1970299210", "W1972514043", "W1979491122", "W1985562847", "W1990487163", "W1990520277", "W1992388470", "W1994679514", "W1998516111", "W1998971866", "W2010038137", "W2010978319", "W2013678879", "W2016579969", "W2021690537", "W2022354436", "W2035282066", "W2038056960", "W2038586807", "W2039845571", "W2041723408", "W2044558623", "W2055402151", "W2055453661", "W2056163848", "W2059499441", "W2060275730", "W2073937000", "W2092324321", "W2096844786", "W2104830962", "W2108257186", "W2116987967", "W2129039984", "W2134607826", "W2136549983", "W2136831156", "W2137390717", "W2138441674", "W2140204532", "W2148971037", "W2150424194", "W2150515509", "W2152346740", "W2163577759", "W2164452916", "W2168691181", "W2172208023", "W2189233644", "W2589467896", "W2590390153", "W2951150209", "W2952805166", "W4230601595"], "baslik": "Structure Based Drug Design of Crizotinib (PF-02341066), a Potent and Selective Dual Inhibitor of Mesenchymal–Epithelial Transition Factor (c-MET) Kinase and Anaplastic Lymphoma Kinase (ALK)", "doi": "https://doi.org/10.1021/jm2007613", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Crizotinib", "Anaplastic lymphoma kinase", "Chemistry", "Cancer research", "Kinase", "Tyrosine kinase", "Tyrosine-kinase inhibitor", "ALK inhibitor"], "kimlik": "W2111254482", "ozet": "Because of the critical roles of aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure of 3 (PHA-665752), bound to c-MET kinase domain, revealed a novel ATP site environment, which served as the target to guide parallel, multiattribute drug design. A novel 2-amino-5-aryl-3-benzyloxypyridine series was created to more effectively make the key interactions achieved with 3. In the novel series, the 2-aminopyridine core allowed a 3-benzyloxy group to reach into the same pocket as the 2,6-dichlorophenyl group of 3 via a more direct vector and thus with a better ligand efficiency (LE). Further optimization of the lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in vitro and in vivo c-MET kinase and ALK inhibition, effective tumor growth inhibition, and good pharmaceutical properties.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["J. Jean Cui", "Michelle Tran‐Dubé", "Hong Shen", "Mitchell D. Nambu", "Pei‐Pei Kung", "Mason Pairish", "Lei Jia", "Jerry Meng", "Lee Funk", "Iriny Botrous", "Michele McTigue", "Neil B. Grodsky"], "yil": 2011}
{"doi": "https://doi.org/10.1038/nchembio.1938", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2189824412"}
{"atif_sayisi": 921, "atiflar": ["W8931042", "W89133559", "W1486597752", "W1496702246", "W1501935523", "W1506509855", "W1513692363", "W1515059043", "W1525154317", "W1528368632", "W1533598873", "W1537062554", "W1537216823", "W1537885139", "W1539281575", "W1545503281", "W1547466369", "W1554485696", "W1557874430", "W1570629413", "W1582473274", "W1583256888", "W1596955093", "W1975642651", "W1984159784", "W2005529016", "W2017499074", "W2018751358", "W2022163051", "W2028078288", "W2033436103", "W2037985807", "W2042414962", "W2050604034", "W2061959038", "W2064801081", "W2074571771", "W2086906852", "W2090940799", "W2092045274", "W2094976314", "W2102431039", "W2121795850", "W2143873575"], "baslik": "Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin.", "doi": "https://doi.org/10.1016/s0021-9258(17)41901-6", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Wortmannin", "Autophosphorylation", "Phosphatidylinositol", "Insulin receptor", "Insulin", "Insulin receptor substrate", "GLUT4", "Kinase"], "kimlik": "W1551443142", "ozet": "Significant activity of phosphatidylinositol 3-kinase (PI 3-kinase) was detected in the membrane fractions, or in the immunoprecipitates prepared with anti-phosphotyrosine antibodies, from rat adipocytes that had been incubated with insulin for 20 min. The PI 3-kinase activity in these preparations as well as in the whole cell lysates of adipocytes not treated with insulin was inhibited by the addition of wortmannin, a fungal metabolite, to the enzyme assay mixture. The inhibition was dependent on the inhibitor concentration with IC50 being less than 10 nM and perfect inhibition at 100 nM. The effect of insulin to induce membrane PI 3-kinase activity was mostly abolished, but its effects to tyrosine-phosphorylate the beta-subunit of the insulin receptor or other cellular substrate proteins including insulin-receptor-substrate-1 were not at all antagonized, by wortmannin added to the cell incubation medium. Insulin stimulation of cellular 2-deoxyglucose uptake and inhibition of isoproterenol-induced lipolysis observable in adipocytes under the same conditions were also antagonized by wortmannin added in the same concentration range as used for the inhibition of insulin-susceptible PI 3-kinase. It is concluded, therefore, that activation of wortmannin-sensitive PI 3-kinase plays a pivotal role in the intracellular signaling pathways arising from the insulin receptor autophosphorylation and leading to certain metabolic responses.", "tam_metin_adresi": "https://doi.org/10.1016/s0021-9258(17)41901-6", "yayinci": "Elsevier BV", "yazarlar": ["Taro Okada", "Y. Kawano", "Tsuneki Sakakibara", "Osamu Hazeki", "M Ui"], "yil": 1994}
{"atif_sayisi": 939, "atiflar": ["W39533467", "W141627170", "W168811426", "W1263601218", "W1531775950", "W1533077869", "W1569865130", "W1701250584", "W1755092205", "W1779286308", "W1874305637", "W1933350662", "W1976419136", "W1979895077", "W1980561538", "W1982186905", "W1986488244", "W1989055139", "W2001453148", "W2019895529", "W2026175788", "W2027960164", "W2038882649", "W2063893852", "W2064047613", "W2069637592", "W2085254573", "W2086702753", "W2088658971", "W2094404156", "W2100960099", "W2106764013", "W2109960839", "W2121808641", "W2123284520", "W2137101013", "W2139984188", "W2150290224", "W2154027407", "W2157617883", "W2169434055", "W2170517479", "W2331400535", "W2344444710", "W2474195763", "W2920878173"], "baslik": "Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Cancer research", "Docetaxel", "Growth inhibition", "Epidermal growth factor receptor", "Medicine", "Pharmacology", "Cancer cell", "Cancer"], "kimlik": "W2163402367", "ozet": "Transforming growth factor alpha (TGF-alpha) is an autocrine growth factor for human cancer. Overexpression of TGF-alpha and its specific receptor, the epidermal growth factor receptor (EGFR), is associated with aggressive disease and poor prognosis. The EGFR has been proposed as a target for anticancer therapy. Compounds that block ligand-induced EGFR activation have been developed. ZD-1839 (Iressa) is a p.o.-active, quinazoline derivative that selectively inhibits the EGFR tyrosine kinase and is under clinical development in cancer patients. The antiproliferative activity of ZD-1839 alone or in combination with cytotoxic drugs differing in mechanism(s) of action, such as cisplatin, carboplatin, oxaliplatin, paclitaxel, docetaxel, doxorubicin, etoposide, topotecan, and raltitrexed, was evaluated in human ovarian (OVCAR-3), breast (ZR-75-1, MCF-10A ras), and colon cancer (GEO) cells that coexpress EGFR and TGF-alpha. ZD-1839 inhibited colony formation in soft agar in a dose-dependent manner in all cancer cell lines. The antiproliferative effect was mainly cytostatic. However, treatment with higher doses resulted in a 2-4-fold increase in apoptosis. A dose-dependent supra-additive increase in growth inhibition was observed when cancer cells were treated with each cytotoxic drug and ZD-1839. The combined treatment markedly enhanced apoptotic cell death induced by single-agent treatment. ZD-1839 treatment of nude mice bearing established human GEO colon cancer xenografts revealed a reversible dose-dependent inhibition of tumor growth because GEO tumors resumed the growth rate of controls at the end of the treatment. In contrast, the combined treatment with a cytotoxic agent, such as topotecan, raltitrexed, or paclitaxel, and ZD-1839 produced tumor growth arrest in all mice. Tumors grew slowly for approximately 4-8 weeks after the end of treatment, when they finally resumed a growth rate similar to controls. GEO tumors reached a size not compatible with normal life in all control mice within 4-6 weeks and in all single agent-treated mice within 6-8 weeks after GEO cell injection. In contrast, 50% of mice treated with ZD-1839 plus topotecan, raltitrexed, or paclitaxel were still alive 10, 12, and 15 weeks after cancer cell injection, respectively. These results demonstrate the antitumor effect of this EGFR-selective tyrosine kinase inhibitor and provide a rationale for its clinical evaluation in combination with cytotoxic drugs.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Fortunato Ciardiello", "R. Caputo", "Roberto Bianco", "Damiano", "G Pomatico", "De Placido S", "Bianco Ar", "Giampaolo Tortora"], "yil": 2000}
{"atif_sayisi": 502, "atiflar": [], "baslik": "K252a is a selective inhibitor of the tyrosine protein kinase activity of the trk family of oncogenes and neurotrophin receptors.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Trk receptor", "Tropomyosin receptor kinase A", "Tropomyosin receptor kinase C", "Tropomyosin receptor kinase B", "Biology", "Receptor tyrosine kinase", "Tyrosine kinase", "Neurotrophin"], "kimlik": "W2282636056", "ozet": "K252a, an efficient serine/threonine protein kinase inhibitor (IC50s of 10 to 30 nM), has been shown to block the neuronal differentiation of rat pheochromocytoma PC12 cells induced by nerve growth factor (NGF). In this report, we demonstrate that K252a is a potent inhibitor (IC50 of 3 nM) of the tyrosine protein kinase activity of the NGF receptor gp140trk, the product of the trk protooncogene. K252a also inhibits the kinase activity of its transforming alleles, the trk oncogenes, and of the related neurotrophin receptors gp145trkB and gp145trkC, the products of the other known members of the trk gene family, trkB and trkC. In contrast, K252a has no effect (even at micromolar concentrations) on other tyrosine protein kinases such as the receptors for EGF and PDGF and the products of the v-src and v-fms oncogenes. In addition, K252a rapidly reverts the transformed phenotype of NIH3T3 cells transformed by either autocrine stimulation of the trk family of receptors by their cognate ligands or by expression of trk oncogenes isolated from human tumors. The selectivity of K252a for the catalytic activity of the trk family of kinases should help to establish the structural basis for the rational design of highly specific tyrosine protein kinase inhibitors.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Peter Tapley", "Fabienne Lamballe", "Mariano Barbacid"], "yil": 1992}
{"atif_sayisi": 559, "atiflar": ["W6823376", "W53659813", "W1527792826", "W1555947589", "W1570362997", "W1875580551", "W1978046076", "W1982958012", "W1986362116", "W1992527405", "W1997937533", "W2001866120", "W2005572521", "W2019612671", "W2019659823", "W2021491196", "W2022309233", "W2038063954", "W2038594687", "W2045278002", "W2046766433", "W2047308859", "W2047980471", "W2049761828", "W2049875806", "W2051788298", "W2055753122", "W2057231488", "W2058138221", "W2075171810", "W2098017074", "W2098601481", "W2104979495", "W2107409046", "W2112820874", "W2124867155", "W2130357785", "W2133733742", "W2140664543", "W2149189904", "W2161071101", "W2170537843", "W2327640792", "W2338614084", "W2341471202", "W2405274657", "W2412315246", "W4229598164", "W4235921012", "W4241442678", "W4295216797"], "baslik": "Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo", "doi": "https://doi.org/10.2337/diabetes.52.3.588", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Glycogen synthase", "Internal medicine", "Endocrinology", "Insulin", "GSK-3", "Insulin resistance", "Glucose uptake", "Glycogen"], "kimlik": "W2109479865", "ozet": "Insulin resistance plays a central role in the development of type 2 diabetes, but the precise defects in insulin action remain to be elucidated. Glycogen synthase kinase 3 (GSK-3) can negatively regulate several aspects of insulin signaling, and elevated levels of GSK-3 have been reported in skeletal muscle from diabetic rodents and humans. A limited amount of information is available regarding the utility of highly selective inhibitors of GSK-3 for the modification of insulin action under conditions of insulin resistance. In the present investigation, we describe novel substituted aminopyrimidine derivatives that inhibit human GSK-3 potently (K(i) < 10 nmol/l) with at least 500-fold selectivity against 20 other protein kinases. These low molecular weight compounds activated glycogen synthase at approximately 100 nmol/l in cultured CHO cells transfected with the insulin receptor and in primary hepatocytes isolated from Sprague-Dawley rats, and at 500 nmol/l in isolated type 1 skeletal muscle of both lean Zucker and ZDF rats. It is interesting that these GSK-3 inhibitors enhanced insulin-stimulated glucose transport in type 1 skeletal muscle from the insulin-resistant ZDF rats but not from insulin-sensitive lean Zucker rats. Single oral or subcutaneous doses of the inhibitors (30-48 mg/kg) rapidly lowered blood glucose levels and improved glucose disposal after oral or intravenous glucose challenges in ZDF rats and db/db mice, without causing hypoglycemia or markedly elevating insulin. Collectively, our results suggest that these selective GSK-3 inhibitors may be useful as acute-acting therapeutics for the treatment of the insulin resistance of type 2 diabetes.", "tam_metin_adresi": null, "yayinci": "American Diabetes Association", "yazarlar": ["David B. Ring", "Kirk W. Johnson", "Erik J. Henriksen", "John M. Nuss", "Dane A. Goff", "Tyson R. Kinnick", "Thokchom Sylvia", "John W. Reeder", "Isa Samuels", "Trina Slabiak", "Allan S. Wagman", "Mary-Ellen Wernette Hammond"], "yil": 2003}
{"atif_sayisi": 2706, "atiflar": ["W49411393", "W948493078", "W1491958169", "W1565643565", "W1569556111", "W1593259671", "W1614508806", "W1651255081", "W1661233179", "W1775749144", "W1969581258", "W1971648429", "W1973614628", "W1988680862", "W1994231412", "W1995532233", "W2010820226", "W2052180430", "W2054733603", "W2064730452", "W2091946486", "W2153435210", "W2183970233", "W2338226312", "W2410835544", "W2410902315", "W4250847391"], "baslik": "Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide-dependent protein kinase and protein kinase C", "doi": "https://doi.org/10.1021/bi00316a032", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Chemical Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Chemical Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Citation", "Icon", "Computer science", "Kinase", "Protein kinase A", "Social media", "Information retrieval", "World Wide Web"], "kimlik": "W1973454785", "ozet": "Naphthalenesulfonamides such as N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) are potent calmodulin (CaM) antagonists and act upon several protein kinases at higher concentration. When the naphthalene ring was replaced by isoquinoline, the derivatives were no longer CaM antagonists but retained the ability to inhibit protein kinases, and some of the derivatives exhibited selective inhibition toward a certain protein kinase. cAMP-dependent, cGMP-dependent, and Ca2+-phospholipid-dependent (protein kinase C) protein kinases were inhibited significantly by addition of 10(-6) M N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (H-8) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7). H-8 was the most active of the inhibitors in this series and inhibited more markedly cyclic nucleotide dependent protein kinases, than other kinases, while the derivative with the sulfonylpiperazine residue (H-7) was the most potent in inhibiting protein kinase C. Apparent Ki values of H-8 were 0.48 and 1.2 microM for cGMP-dependent and cAMP-dependent protein kinases, respectively, and the Ki value of H-7 for protein kinase C was 6 microM. Both the holoenzyme and the catalytic subunit (or fragment), which is active without an enzyme activator, are susceptible to these compounds with a similar concentration dependency, thereby indicating that the inhibitory effect is attributed to the direct interaction of the compound with the active center of the enzyme but not with the enzyme activator. The inhibitions were freely reversible and of the competitive type with respect to ATP and of the noncompetitive type with respect to the phosphate acceptor.(ABSTRACT TRUNCATED AT 250 WORDS)", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Hiroyoshi Hidaka", "Masaki Inagaki", "Sachiyo Kawamoto", "Yasuharu Sasaki"], "yil": 1984}
{"doi": "https://doi.org/10.1016/s0163-7258(98)00044-8", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W1983790923"}
{"atif_sayisi": 2717, "atiflar": ["W1500873351", "W1559986791", "W1572416479", "W1631361623", "W1854798937", "W1968590447", "W1973766879", "W1976462601", "W1978798502", "W1982390204", "W1985399284", "W1989480480", "W2001521752", "W2010955929", "W2031452885", "W2034658941", "W2051538397", "W2066696278", "W2069132844", "W2111295274", "W2342902491", "W2413160353"], "baslik": "A synthetic inhibitor of the mitogen-activated protein kinase cascade.", "doi": "https://doi.org/10.1073/pnas.92.17.7686", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["MAPK/ERK pathway", "Kinase", "Mitogen-activated protein kinase", "Cell biology", "MAPK cascade", "Phosphorylation", "Protein kinase A", "Chemistry"], "kimlik": "W1971915141", "ozet": "Treatment of cells with a variety of growth factors triggers a phosphorylation cascade that leads to activation of mitogen-activated protein kinases (MAPKs, also called extracellular signal-regulated kinases, or ERKs). We have identified a synthetic inhibitor of the MAPK pathway. PD 098059 [2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one] selectively inhibited the MAPK-activating enzyme, MAPK/ERK kinase (MEK), without significant inhibitory activity of MAPK itself. Inhibition of MEK by PD 098059 prevented activation of MAPK and subsequent phosphorylation of MAPK substrates both in vitro and in intact cells. Moreover, PD 098059 inhibited stimulation of cell growth and reversed the phenotype of ras-transformed BALB 3T3 mouse fibroblasts and rat kidney cells. These results indicate that the MAPK pathway is essential for growth and maintenance of the ras-transformed phenotype. Further, PD 098059 is an invaluable tool that will help elucidate the role of the MAPK cascade in a variety of biological settings.", "tam_metin_adresi": null, "yayinci": "National Academy of Sciences", "yazarlar": ["David T. Dudley", "Long Pang", "Stuart J. Decker", "Alexander J. Bridges", "Alan R. Saltiel"], "yil": 1995}
{"doi": "https://doi.org/10.1016/s0959-8049(02)80599-8", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W1965260090"}
{"atif_sayisi": 504, "atiflar": ["W11727989", "W39467412", "W1541491219", "W1543268153", "W1546577360", "W1953884850", "W1963579146", "W1963891523", "W1981856729", "W1983742719", "W2001853125", "W2002714006", "W2004774286", "W2005041472", "W2019836798", "W2030500412", "W2031541885", "W2036735258", "W2047476474", "W2047510068", "W2054290966", "W2064534470", "W2065628269", "W2074775218", "W2075790601", "W2080500939", "W2088123597", "W2089756110", "W2097373408", "W2101306957", "W2118471405", "W2120404631", "W2122696814", "W2126524003", "W2132163449", "W2147535764", "W2149259234", "W2149594557", "W2162147795", "W2170191698", "W2170444924", "W2308973955", "W2330934614", "W2437267759", "W3121948843", "W4285719527", "W6632554305", "W6640879643", "W6666721012", "W6697928590", "W6717788465"], "baslik": "AZD4547: An Orally Bioavailable, Potent, and Selective Inhibitor of the Fibroblast Growth Factor Receptor Tyrosine Kinase Family", "doi": "https://doi.org/10.1158/0008-5472.can-11-3034", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Fibroblast growth factor receptor", "Cancer research", "Tyrosine kinase", "Receptor tyrosine kinase", "Pharmacology", "Fibroblast growth factor", "Tyrosine-kinase inhibitor", "Fibroblast growth factor receptor 1"], "kimlik": "W2019711215", "ozet": "The fibroblast growth factor (FGF) signaling axis is increasingly implicated in tumorigenesis and chemoresistance. Several small-molecule FGF receptor (FGFR) kinase inhibitors are currently in clinical development; however, the predominant activity of the most advanced of these agents is against the kinase insert domain receptor (KDR), which compromises the FGFR selectivity. Here, we report the pharmacologic profile of AZD4547, a novel and selective inhibitor of the FGFR1, 2, and 3 tyrosine kinases. AZD4547 inhibited recombinant FGFR kinase activity in vitro and suppressed FGFR signaling and growth in tumor cell lines with deregulated FGFR expression. In a representative FGFR-driven human tumor xenograft model, oral administration of AZD4547 was well tolerated and resulted in potent dose-dependent antitumor activity, consistent with plasma exposure and pharmacodynamic modulation of tumor FGFR. Importantly, at efficacious doses, no evidence of anti-KDR-related effects were observed, confirming the in vivo FGFR selectivity of AZD4547. Taken together, our findings show that AZD4547 is a novel selective small-molecule inhibitor of FGFR with potent antitumor activity against FGFR-deregulated tumors in preclinical models. AZD4547 is under clinical investigation for the treatment of FGFR-dependent tumors.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Paul R. Gavine", "Lorraine Mooney", "Elaine Kilgour", "Andrew P. Thomas", "Katherine Al-Kadhimi", "Sarah Beck", "Claire Rooney", "Tanya Coleman", "Dawn Baker", "Martine J. Mellor", "A. Nigel Brooks", "Teresa Klinowska"], "yil": 2012}
{"doi": "https://doi.org/10.1038/nchembio.1582", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2093859044"}
{"atif_sayisi": 517, "atiflar": ["W194331471", "W1529087905", "W1560464036", "W1573213785", "W1605269201", "W1969375092", "W1969543057", "W1981387221", "W1981619037", "W1988769784", "W1989174349", "W1990617217", "W1996165605", "W1996547558", "W2010839009", "W2013123720", "W2017975463", "W2018205014", "W2024859791", "W2031728328", "W2032566634", "W2034269086", "W2036521316", "W2059468328", "W2060346337", "W2073206818", "W2074631079", "W2077804275", "W2077813812", "W2081681244", "W2085173493", "W2087861588", "W2091297863", "W2098671913", "W2119073457", "W2121723225", "W2128456899", "W2129381779", "W2129881449", "W2148990487", "W2151575257", "W2153969389", "W2155737059", "W2159023635", "W2161696113", "W2168438265", "W2168759561", "W2273462154", "W2416705592", "W4254073170", "W6658677740", "W6716632361"], "baslik": "CX-4945, an Orally Bioavailable Selective Inhibitor of Protein Kinase CK2, Inhibits Prosurvival and Angiogenic Signaling and Exhibits Antitumor Efficacy", "doi": "https://doi.org/10.1158/0008-5472.can-10-1893", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Protein kinase B", "Cancer cell", "PI3K/AKT/mTOR pathway", "Cancer research", "Pharmacology", "Kinase", "Chemistry", "Oncogene"], "kimlik": "W2088938650", "ozet": "Malignant transformation and maintenance of the malignant phenotype depends on oncogenic and non-oncogenic proteins that are essential to mediate oncogene signaling and to support the altered physiologic demands induced by transformation. Protein kinase CK2 supports key prosurvival signaling pathways and represents a prototypical non-oncogene. In this study, we describe CX-4945, a potent and selective orally bioavailable small molecule inhibitor of CK2. The antiproliferative activity of CX-4945 against cancer cells correlated with expression levels of the CK2α catalytic subunit. Attenuation of PI3K/Akt signaling by CX-4945 was evidenced by dephosphorylation of Akt on the CK2-specific S129 site and the canonical S473 and T308 regulatory sites. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent hypoxia-induced factor 1 alpha (HIF-1α) transcription in cancer cells. When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145). The observed antiproliferative and anti-angiogenic responses to CX-4945 in tumor cells and endothelial cells collectively illustrate that this compound exerts its antitumor effects through inhibition of CK2-dependent signaling in multiple pathways. Finally, CX-4945 is the first orally bioavailable small molecule inhibitor of CK2 to advance into human clinical trials, thereby paving the way for an entirely new class of targeted treatment for cancer.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Adam Siddiqui-Jain", "Denis Drygin", "Nicole Streiner", "Peter Chua", "Fabrice Pierre", "Sean O’Brien", "Josh Bliesath", "Mayuko Omori", "Nanni Huser", "Caroline B. Ho", "Chris Proffitt", "Michael K. Schwaebe"], "yil": 2010}
{"atif_sayisi": 2570, "atiflar": ["W163209956", "W1521372932", "W1530284699", "W1572174728", "W1798720605", "W1961508547", "W1963792000", "W1970581527", "W1971304464", "W1972145919", "W1973967947", "W1976305765", "W1979129905", "W1984903682", "W1986559713", "W1993351141", "W2005701369", "W2009386000", "W2015557220", "W2022185380", "W2032731042", "W2038570411", "W2053560001", "W2057094603", "W2058588605", "W2064265900", "W2070044720", "W2086402424", "W2094407798", "W2101937406", "W2112294647", "W2112740572", "W2116071377", "W2118897660", "W2119807130", "W2148244668", "W2152808118", "W2155280531", "W2278666899", "W2418613038", "W2434896399", "W2969273703", "W4235884942", "W4247673683", "W4285719527", "W6979169529"], "baslik": "SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase", "doi": "https://doi.org/10.1073/pnas.251194298", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "c-jun", "Tumor necrosis factor alpha", "Molecular biology", "Apoptosis", "Biology", "Protein kinase A", "Cell biology"], "kimlik": "W2096931514", "ozet": "Jun N-terminal kinase (JNK) is a stress-activated protein kinase that can be induced by inflammatory cytokines, bacterial endotoxin, osmotic shock, UV radiation, and hypoxia. We report the identification of an anthrapyrazolone series with significant inhibition of JNK1, -2, and -3 (K(i) = 0.19 microM). SP600125 is a reversible ATP-competitive inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-gamma, TNF-alpha, and prevented the activation and differentiation of primary human CD4 cell cultures. In animal studies, SP600125 blocked (bacterial) lipopolysaccharide-induced expression of tumor necrosis factor-alpha and inhibited anti-CD3-induced apoptosis of CD4(+) CD8(+) thymocytes. Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer.", "tam_metin_adresi": null, "yayinci": "National Academy of Sciences", "yazarlar": ["Brydon L. Bennett", "Dennis T. Sasaki", "Brion W. Murray", "E C O'Leary", "Steve T. Sakata", "Weiming Xu", "Jim Leisten", "Aparna Motiwala", "Steve Pierce", "Yoshitaka Satoh", "Shripad S. Bhagwat", "Anthony M. Manning"], "yil": 2001}
{"atif_sayisi": 383, "atiflar": ["W37325828", "W1430273632", "W1536079196", "W1539796472", "W1561493617", "W1630547983", "W1970131417", "W1975866732", "W1983072511", "W1986194005", "W1992546098", "W1993584147", "W1998777645", "W1999804481", "W2001641653", "W2010040669", "W2028691987", "W2033711687", "W2038840577", "W2046713135", "W2052221882", "W2059552745", "W2065088072", "W2067405360", "W2077163123", "W2097493124", "W2100794900", "W2100996687", "W2107200488", "W2110735029", "W2112380414", "W2114462664", "W2118105104", "W2135596119", "W2135839939", "W2142682878", "W2156480395", "W2158769524", "W2159031005", "W2159695799", "W2165988906", "W2170718796", "W2171179595", "W2271717271", "W2283549843", "W2310034942"], "baslik": "Antitumor Activity and Pharmacology of a Selective Focal Adhesion Kinase Inhibitor, PF-562,271", "doi": "https://doi.org/10.1158/0008-5472.can-07-5155", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Focal adhesion", "In vivo", "Kinase", "Phosphorylation", "Chemistry", "Cancer research", "Tyrosine kinase", "Pharmacology"], "kimlik": "W2065088072", "ozet": "Cancer cells are characterized by the ability to grow in an anchorage-independent manner. The activity of the nonreceptor tyrosine kinase, focal adhesion kinase (FAK), is thought to contribute to this phenotype. FAK localizes in focal adhesion plaques and has a role as a scaffolding and signaling protein for other adhesion molecules. Recent studies show a strong correlation between increased FAK expression and phosphorylation status and the invasive phenotype of aggressive human tumors. PF-562,271 is a potent, ATP-competitive, reversible inhibitor of FAK and Pyk2 catalytic activity with a IC(50) of 1.5 and 14 nmol/L, respectively. Additionally, PF-562,271 displayed robust inhibition in an inducible cell-based assay measuring phospho-FAK with an IC(50) of 5 nmol/L. PF-562,271 was evaluated against multiple kinases and displays >100x selectivity against a long list of nontarget kinases. PF-562,271 inhibits FAK phosphorylation in vivo in a dose-dependent fashion (calculated EC(50) of 93 ng/mL, total) after p.o. administration to tumor-bearing mice. In vivo inhibition of FAK phosphorylation (>50%) was sustained for >4 hours with a single p.o. dose of 33 mg/kg. Antitumor efficacy and regressions were observed in multiple human s.c. xenograft models. No weight loss, morbidity, or mortality were observed in any in vivo experiment. Tumor growth inhibition was dose and drug exposure dependent. Taken together, these data show that kinase inhibition with an ATP-competitive small molecule inhibitor of FAK decreases the phospho-status in vivo, resulting in robust antitumor activity.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["W. Gregory Roberts", "Ethan Ung", "Pamela Whalen", "Beth Cooper", "Catherine A. Hulford", "Christofer Autry", "Daniel Richter", "Earling Emerson", "Jing Lin", "John C. Kath", "Kevin Coleman", "Lili Yao"], "yil": 2008}
{"doi": "https://doi.org/10.1016/s0014-5793(01)02404-8", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W1993148712"}
{"atif_sayisi": 377, "atiflar": ["W1538925875", "W1540390830", "W1545201063", "W1567624342", "W1756593307", "W1966164508", "W1967550038", "W1969255091", "W1971468364", "W1977971438", "W1980370645", "W1983435458", "W1985039245", "W1986333080", "W1989060543", "W1997332832", "W2002939681", "W2005404705", "W2007225446", "W2007618242", "W2011805684", "W2015265007", "W2017000348", "W2021464180", "W2021722888", "W2030205108", "W2038143561", "W2040788683", "W2041924725", "W2043213848", "W2046847991", "W2052221882", "W2053092498", "W2065113058", "W2083647300", "W2084810833", "W2097348395", "W2104373322", "W2124867155", "W2129677617", "W2131124255", "W2132570158", "W2138778824", "W2143292283", "W2153250061", "W2154910634", "W2155230284", "W2155591132", "W2167040797", "W2314977263", "W2326407786", "W2346343001", "W2401829656", "W2481759650", "W4235408944"], "baslik": "Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases", "doi": "https://doi.org/10.1021/jm031016d", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["GSK-3", "Kinase", "Cyclin-dependent kinase", "Chemistry", "Glycogen synthase", "Biochemistry", "Cyclin-dependent kinase 2", "Enzyme"], "kimlik": "W1970197612", "ozet": "Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Panagiotis Polychronopoulos", "Prokopios Magiatis", "Alexios‐Léandros Skaltsounis", "Vassilios Myrianthopoulos", "Emmanuel Mikros", "Aldo Tarricone", "Andrea Musacchio", "S. Mark Roe", "Laurence H. Pearl", "Maryse Leost", "Paul Greengard", "Laurent Meijer"], "yil": 2004}
{"atif_sayisi": 383, "atiflar": ["W1483800737", "W1493948383", "W1518868828", "W1518872013", "W1533874578", "W1576671418", "W1595529083", "W1597640694", "W1597893467", "W1634621704", "W1970334202", "W1972223792", "W1973466803", "W1983348926", "W1991714532", "W1992660699", "W1993282564", "W2000819798", "W2015249790", "W2023972740", "W2036628331", "W2041556575", "W2051106587", "W2051315704", "W2072567218", "W2076660235", "W2085812290", "W2089330962", "W2089475281", "W2099628115", "W2136637563", "W2151427994", "W2160332942", "W2166016248"], "baslik": "A Protein Kinase C Translocation Inhibitor as an Isozyme-selective Antagonist of Cardiac Function", "doi": "https://doi.org/10.1074/jbc.271.40.24962", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Protein kinase C", "Isozyme", "Chromosomal translocation", "Biology", "Biochemistry", "Receptor", "Cell biology", "Protein kinase A"], "kimlik": "W2061052988", "ozet": "Protein kinase C (PKC) isozymes translocate to unique subcellular sites following activation. We previously suggested that translocation of activated isozymes is required for their function and that in addition to binding to lipids, translocation involves binding of the activated isozymes to specific anchoring proteins (receptors for activated protein kinase C. Using cultured cardiomyocytes we identified inhibitors, the V1 fragment of epsilonPKC (epsilonV1), and an 8-amino acid peptide derived from it that selectively inhibited the translocation of epsilonPKC. Inhibition of epsilonPKC translocation but not inhibition of delta or betaPKC translocation specifically blocked phorbol ester- or norepinephrine-mediated regulation of contraction. These isozyme-selective translocation inhibitors provide novel tools to determine the function of individual PKC isozymes in intact cells.", "tam_metin_adresi": "https://doi.org/10.1074/jbc.271.40.24962", "yayinci": "Elsevier BV", "yazarlar": ["John A. Johnson", "Mary O. Gray", "Che-Hong Chen", "Daria Mochly‐Rosen"], "yil": 1996}
{"doi": "https://doi.org/10.1016/j.bmcl.2013.05.007", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2126839635"}
{"doi": "https://doi.org/10.1016/j.chembiol.2008.03.005", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2155087173"}
{"atif_sayisi": 243, "atiflar": ["W112191695", "W1506411711", "W1508960621", "W1523210175", "W1537623701", "W1969543057", "W1970197743", "W1971294233", "W1972603998", "W1978517331", "W1987767964", "W1988791458", "W1990617217", "W1993148712", "W1995134802", "W2003858378", "W2007909244", "W2011971841", "W2012060632", "W2021028340", "W2028428863", "W2030205108", "W2031728328", "W2046822015", "W2048736992", "W2052750950", "W2059548925", "W2060479161", "W2074506458", "W2074631079", "W2081685417", "W2081723980", "W2087267008", "W2087372366", "W2091297863", "W2092678097", "W2093611899", "W2099937543", "W2124848654", "W2129381779", "W2129881449", "W2132785681", "W2139445161", "W2150099809", "W2150121030", "W2158041398", "W2160842779", "W2168759561", "W2172171459", "W2178853193", "W2325130175", "W4247904703"], "baslik": "The selectivity of inhibitors of protein kinase CK2: an update", "doi": "https://doi.org/10.1042/bj20080309", "gerekce": "telifli görünüyor (lisans=`other-oa`, yayıncı=`Portland Press`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "other-oa", "yayinci": "Portland Press"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Casein kinase 2", "Threonine", "DYRK1A", "Benzimidazole", "Casein kinase 1", "Chemistry", "Biochemistry"], "kimlik": "W2011219963", "ozet": "CK2 (casein kinase 2) is a very pleiotropic serine/threonine protein kinase whose abnormally high constitutive activity has often been correlated to pathological conditions with special reference to neoplasia. The two most widely used cell permeable CK2 inhibitors, TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole), are marketed as quite specific CK2 blockers. In the present study we show, by using a panel of approx. 80 protein kinases, that DMAT and its parent compound TBI (or TBBz; 4,5,6,7-tetrabromo-1H-benzimidazole) are potent inhibitors of several other kinases, with special reference to PIM (provirus integration site for Moloney murine leukaemia virus)1, PIM2, PIM3, PKD1 (protein kinase D1), HIPK2 (homeodomain-interacting protein kinase 2) and DYRK1a (dual-specificity tyrosine-phosphorylated and -regulated kinase 1a). In contrast, TBB is significantly more selective toward CK2, although it also inhibits PIM1 and PIM3. In an attempt to improve selectivity towards CK2 a library of 68 TBB/TBI-related compounds have been tested for their ability to discriminate between CK2, PIM1, HIPK2 and DYRK1a, ending up with seven compounds whose efficacy toward CK2 is markedly higher than that toward the second most inhibited kinase. Two of these, K64 (3,4,5,6,7-pentabromo-1H-indazole) and K66 (1-carboxymethyl-2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole), display an overall selectivity much higher than TBB and DMAT when tested on a panel of 80 kinases and display similar efficacy as inducers of apoptosis.", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Mario A. Pagano", "Jenny Bain", "Zygmunt Kazimierczuk", "Stefania Sarno", "Maria Ruzzene", "Giovanni Di Maira", "Matthew Elliott", "Andrzej Orzeszko", "Giorgio Cozza", "Flavio Meggio", "Lorenzo A. Pinna"], "yil": 2008}
{"atif_sayisi": 497, "atiflar": ["W83231304", "W86262156", "W90465349", "W117902596", "W1261881945", "W1263733664", "W1506256987", "W1577036237", "W1649526546", "W1928129824", "W1972607682", "W1973966923", "W1985562847", "W1995862211", "W2005092992", "W2007904495", "W2007941427", "W2012792646", "W2014105735", "W2018672261", "W2019573100", "W2021452013", "W2022527563", "W2023586869", "W2030410158", "W2042323503", "W2042919832", "W2048097275", "W2048613455", "W2049759529", "W2054042846", "W2059950450", "W2067297743", "W2075081031", "W2087352606", "W2093999584", "W2101774275", "W2113045327", "W2121371052", "W2121571446", "W2132755748", "W2134755472", "W2139440398", "W2143984112", "W2149902890", "W2151812232", "W2166927748", "W2323767042", "W2328693672", "W2330176638", "W2406276138"], "baslik": "A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Hepatocyte growth factor", "C-Met", "Tyrosine kinase", "Tyrosine phosphorylation", "Cancer research", "Phosphorylation", "Receptor tyrosine kinase", "Protein kinase B"], "kimlik": "W2137390717", "ozet": "The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been implicated in the development and progression of several human cancers and are attractive targets for cancer therapy. PHA-665752 was identified as a small molecule, ATP-competitive, active-site inhibitor of the catalytic activity of c-Met kinase (K(i) 4 nM). PHA-665752 also exhibited >50-fold selectivity for c-Met compared with a panel of diverse tyrosine and serine-threonine kinases. In cellular studies, PHA-665752 potently inhibited HGF-stimulated and constitutive c-Met phosphorylation, as well as HGF and c-Met-driven phenotypes such as cell growth (proliferation and survival), cell motility, invasion, and/or morphology of a variety of tumor cells. In addition, PHA-665752 inhibited HGF-stimulated or constitutive phosphorylation of mediators of downstream signal transduction of c-Met, including Gab-1, extracellular regulated kinase, Akt, signal transducer and activator of transcription 3, phospholipase C gamma, and focal adhesion kinase, in multiple tumor cell lines in a pattern correlating to the phenotypic response of a given tumor cell. In in vivo studies, a single dose of PHA-665752 inhibited c-Met phosphorylation in tumor xenografts for up to 12 h. Inhibition of c-Met phosphorylation was associated with dose-dependent tumor growth inhibition/growth delay over a repeated administration schedule at well-tolerated doses. Interestingly, potent cytoreductive activity was demonstrated in a gastric carcinoma xenograft model. Collectively, these results demonstrate the feasibility of selectively targeting c-Met with ATP-competitive small-molecules and suggest the therapeutic potential of targeting c-Met in human cancers.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["James G. Christensen", "Randall Schreck", "Jon Burrows", "Poonam A. Kuruganti", "Emily Chan", "Phuong Le", "Jeffrey Chen", "Xueyan Wang", "Lany Ruslim", "Robert A. Blake", "Kenneth E. Lipson", "John Ramphal"], "yil": 2003}
{"atif_sayisi": 669, "atiflar": [], "baslik": "Vascular Endothelial Growth Factor–Induced Retinal Permeability Is Mediated by Protein Kinase C In Vivo and Suppressed by an Orally Effective β-Isoform–Selective Inhibitor", "doi": "https://doi.org/10.2337/diab.46.9.1473", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Diabetes Association`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Diabetes Association"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Vascular permeability", "Protein kinase C", "Vascular endothelial growth factor", "Retinal", "In vivo", "Diabetic retinopathy", "Vascular endothelial growth factor A", "Gene isoform"], "kimlik": "W1988143227", "ozet": "Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In these studies, we demonstrate that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in the retina at concentrations observed clinically, inducing membrane translocation of PKC isoforms alpha, betaII, and delta and >threefold increases in retinal vasopermeability in vivo. The effect of VEGF on retinal vascular permeability appears to be mediated predominantly by the beta-isoform of PKC with >95% inhibition of VEGF-induced permeability by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated effects. These studies represent the first direct demonstration that VEGF can increase intraocular vascular permeability through activation of PKC in vivo and suggest that oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficacious for the treatment of VEGF-associated ocular disorders such as diabetic retinopathy.", "tam_metin_adresi": null, "yayinci": "American Diabetes Association", "yazarlar": ["Lloyd Paul Aiello", "Sven–Erik Bursell", "Allen C. Clermont", "Elia J. Duh", "Hidehiro Ishii", "Chikako Takagi", "Fumi Mori", "Thomas A. Ciulla", "Kirk Ways", "Michael R. Jirousek", "Lois E. H. Smith", "George L. King"], "yil": 1997}
{"atif_sayisi": 555, "atiflar": ["W171742669", "W1495945591", "W1511853133", "W1607701774", "W1684701053", "W1967600348", "W1969346834", "W1971001418", "W1971574117", "W1980627836", "W2003344188", "W2003445065", "W2006612491", "W2007686629", "W2007927573", "W2012634952", "W2016569548", "W2042198997", "W2046142904", "W2057104738", "W2058719858", "W2072212283", "W2079068389", "W2079309427", "W2092109670", "W2095726706", "W2098012576", "W2100368880", "W2104592492", "W2106382644", "W2107537216", "W2117511143", "W2117716725", "W2125859388", "W2126073113", "W2126127142", "W2129110050", "W2132089284", "W2133651123", "W2136357864", "W2137713702", "W2140012510", "W2140088548", "W2144348878", "W2146012957", "W2148299252", "W2149942973", "W2151665064", "W2153125007", "W2164578622", "W2170253702", "W2170743542", "W2400431328", "W6606989661", "W6651312512", "W6680067882", "W6712941501"], "baslik": "R428, a Selective Small Molecule Inhibitor of Axl Kinase, Blocks Tumor Spread and Prolongs Survival in Models of Metastatic Breast Cancer", "doi": "https://doi.org/10.1158/0008-5472.can-09-2997", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Metastasis", "Cancer research", "Metastatic breast cancer", "Medicine", "Cancer", "AXL receptor tyrosine kinase", "Angiogenesis", "Receptor tyrosine kinase"], "kimlik": "W2122375037", "ozet": "Accumulating evidence suggests important roles for the receptor tyrosine kinase Axl in cancer progression, invasion, metastasis, drug resistance, and patient mortality, highlighting Axl as an attractive target for therapeutic development. We have generated and characterized a potent and selective small-molecule inhibitor, R428, that blocks the catalytic and procancerous activities of Axl. R428 inhibits Axl with low nanomolar activity and blocked Axl-dependent events, including Akt phosphorylation, breast cancer cell invasion, and proinflammatory cytokine production. Pharmacologic investigations revealed favorable exposure after oral administration such that R428-treated tumors displayed a dose-dependent reduction in expression of the cytokine granulocyte macrophage colony-stimulating factor and the epithelial-mesenchymal transition transcriptional regulator Snail. In support of an earlier study, R428 inhibited angiogenesis in corneal micropocket and tumor models. R428 administration reduced metastatic burden and extended survival in MDA-MB-231 intracardiac and 4T1 orthotopic (median survival, >80 days compared with 52 days; P < 0.05) mouse models of breast cancer metastasis. Additionally, R428 synergized with cisplatin to enhance suppression of liver micrometastasis. Our results show that Axl signaling regulates breast cancer metastasis at multiple levels in tumor cells and tumor stromal cells and that selective Axl blockade confers therapeutic value in prolonging survival of animals bearing metastatic tumors.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Sacha J. Holland", "Alison Pan", "Christian Franci", "Yuanming Hu", "Betty Chang", "Weiqun Li", "Matt Duan", "Allan Torneros", "Jiaxin Yu", "Thilo J. Heckrodt", "Jing Zhang", "Pingyu Ding"], "yil": 2010}
{"doi": "https://doi.org/10.1038/sj.bjc.6605366", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2069417222"}
{"atif_sayisi": 491, "atiflar": ["W1967164401", "W1992388470", "W1999015953", "W2017091728", "W2023597265", "W2032359283", "W2064973618", "W2066498455", "W2095140485", "W2114654929", "W2170050478", "W2329862672"], "baslik": "Synthesis and Biological Evaluations of 3-Substituted Indolin-2-ones: A Novel Class of Tyrosine Kinase Inhibitors That Exhibit Selectivity toward Particular Receptor Tyrosine Kinases", "doi": "https://doi.org/10.1021/jm980123i", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Chemistry", "Receptor tyrosine kinase", "Selectivity", "Autophosphorylation", "Tyrosine kinase", "Tyrosine", "Stereochemistry", "Structure–activity relationship"], "kimlik": "W1969855058", "ozet": "3-Substituted indolin-2-ones have been designed and synthesized as a novel class of tyrosine kinase inhibitors which exhibit selectivity toward different receptor tyrosine kinases (RTKs). These compounds have been evaluated for their relative inhibitory properties against a panel of RTKs in intact cells. By modifying the 3-substituted indolin-2-ones, we have identified compounds which showed selective inhibition of the ligand-dependent autophosphorylation of various RTKs at submicromolar levels in cells. Structure-activity analysis for these compounds and their relative potency and selectivity to inhibit particular RTKs has determined that (1) 3-[(five-membered heteroaryl ring)methylidenyl]indolin-2-ones are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C-3 position of indolin-2-ones showed high selectivity toward the EGF and Her-2 RTKs, and (3) the compound containing an extended side chain at the C-3 position of the indolin-2-one (16) exhibited high potency and selectivity when tested against the PDGF and VEGF (Flk-1) RTKs. Recent published crystallographic data for two of these 3-substituted indolin-2-ones provides a rationale to suggest that these compounds may bind in the ATP binding pocket of RTKs. The structure-activity analysis supports the use of subsets of these compounds as specific chemical leads for the development of RTK-specific drugs with broad application for the treatment of human diseases.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Li Sun", "Ngoc Quang Tran", "Flora Tang", "Harald App", "Peter Hirth", "Gerald McMahon", "Cho Tang"], "yil": 1998}
{"doi": "https://doi.org/10.1038/nm.2091", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2115655607"}
{"atif_sayisi": 358, "atiflar": ["W1568060924", "W1977924803", "W1979308791", "W1980577287", "W1982209220", "W2016462887", "W2029335488", "W2033923680", "W2046083187", "W2046109468", "W2071156666", "W2073754955", "W2097373408", "W2103054294", "W2106942695", "W2109196755", "W2128553601", "W2136284645", "W2150703483", "W2163978496", "W2166470703", "W2167382061"], "baslik": "AZD1152, a Selective Inhibitor of Aurora B Kinase, Inhibits Human Tumor Xenograft Growth by Inducing Apoptosis", "doi": "https://doi.org/10.1158/1078-0432.ccr-06-2979", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Aurora B kinase", "Apoptosis", "Cancer research", "Biology", "Aurora inhibitor", "Cell cycle", "Medicine", "Pharmacology"], "kimlik": "W2153850465", "ozet": "PURPOSE: In the current study, we examined the in vivo effects of AZD1152, a novel and specific inhibitor of Aurora kinase activity (with selectivity for Aurora B). EXPERIMENTAL DESIGN: The pharmacodynamic effects and efficacy of AZD1152 were determined in a panel of human tumor xenograft models. AZD1152 was dosed via several parenteral (s.c. osmotic mini-pump, i.p., and i.v.) routes. RESULTS: AZD1152 potently inhibited the growth of human colon, lung, and hematologic tumor xenografts (mean tumor growth inhibition range, 55% to > or =100%; P < 0.05) in immunodeficient mice. Detailed pharmacodynamic analysis in colorectal SW620 tumor-bearing athymic rats treated i.v. with AZD1152 revealed a temporal sequence of phenotypic events in tumors: transient suppression of histone H3 phosphorylation followed by accumulation of 4N DNA in cells (2.4-fold higher compared with controls) and then an increased proportion of polyploid cells (>4N DNA, 2.3-fold higher compared with controls). Histologic analysis showed aberrant cell division that was concurrent with an increase in apoptosis in AZD1152-treated tumors. Bone marrow analyses revealed transient myelosuppression with the drug that was fully reversible following cessation of AZD1152 treatment. CONCLUSIONS: These data suggest that selective targeting of Aurora B kinase may be a promising therapeutic approach for the treatment of a range of malignancies. In addition to the suppression of histone H3 phosphorylation, determination of tumor cell polyploidy and apoptosis may be useful biomarkers for this class of therapeutic agent. AZD1152 is currently in phase I trials.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Robert W. Wilkinson", "Rajesh Odedra", "Simon P. Heaton", "Stephen R. Wedge", "Nicholas Keen", "Claire Crafter", "John R. Foster", "Madeleine C. Brady", "Alison Bigley", "Elaine Brown", "Kate F. Byth", "Nigel Barrass"], "yil": 2007}
{"atif_sayisi": 317, "atiflar": ["W1549962936", "W1595397037", "W1963834943", "W1981071904", "W1993449698", "W1996926003", "W2000678775", "W2003007879", "W2008161863", "W2010938884", "W2018548034", "W2019380162", "W2022589671", "W2026377273", "W2031449170", "W2045972295", "W2047231993", "W2053310582", "W2056142105", "W2061171666", "W2070482516", "W2071600103", "W2078702640", "W2090542818", "W2091423973", "W2092113592", "W2096273281", "W2108091182", "W2117773251", "W2118947805", "W2120675908", "W2121559592", "W2129916653", "W2136584723", "W2140636998", "W2147336880", "W2149902537", "W2164422031", "W2165308436", "W2417709348", "W6684342443"], "baslik": "Pharmacology and Antitumor Activity of ABC294640, a Selective Inhibitor of Sphingosine Kinase-2", "doi": "https://doi.org/10.1124/jpet.109.163444", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Sphingosine kinase", "Pharmacology", "Sphingosine kinase 1", "Sphingosine", "Kinase", "Chemistry"], "kimlik": "W2163885294", "ozet": null, "tam_metin_adresi": null, "yayinci": "American Society for Pharmacology and Experimental Therapeutics", "yazarlar": ["Kevin J. French", "Yan Zhuang", "Lynn W. Maines", "Peng Gao", "Wenxue Wang", "Vladimir Beljanski", "John J. Upson", "Cecelia L. Green", "Staci N. Keller", "Charles D. Smith"], "yil": 2010}
{"doi": "https://doi.org/10.1089/154065804323056558", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Mary Ann Liebert, Inc.` (P4310320443) `SAGE Publishing` grubuna ait: kullanım koşullarında ticari TDM açıkça hariç tutulmuş · 3,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Mary Ann Liebert, Inc.` (P4310320443) `SAGE Publishing` grubuna ait: kullanım koşullarında ticari TDM açıkça hariç tutulmuş · 3,2M eser"}, "izin": "ENGELLI", "kimlik": "W2112499029"}
{"atif_sayisi": 835, "atiflar": ["W101504470", "W1590794385", "W1659692600", "W1939364580", "W1972004339", "W1978346197", "W2002502311", "W2010174111", "W2015293591", "W2021716162", "W2030444396", "W2038882649", "W2040264246", "W2045406970", "W2045993433", "W2057458801", "W2058992264", "W2064047613", "W2076667824", "W2088597803", "W2109960839", "W2114291028", "W2135836172", "W2135938911", "W2139248078", "W2142661339", "W2155977433", "W2163402367", "W2167368130", "W2291334052", "W2398640414", "W2475324104", "W4240064739"], "baslik": "Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types", "doi": "https://doi.org/10.1200/jco.2002.03.100", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`Lippincott Williams & Wilkins`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "Lippincott Williams & Wilkins"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Medicine", "Tolerability", "Pharmacokinetics", "Pharmacodynamics", "Gefitinib", "Rash", "Epidermal growth factor receptor", "Internal medicine"], "kimlik": "W2126314379", "ozet": "PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.", "tam_metin_adresi": null, "yayinci": "Lippincott Williams & Wilkins", "yazarlar": ["José Baselga", "Danny Rischin", "Malcolm Ranson", "Hilary Calvert", "Éric Raymond", "D G Kieback", "Stan B. Kaye", "Luca Gianni", "Adrian L. Harris", "Thomas Björk", "Steven D. Averbuch", "A. Feyereislova"], "yil": 2002}
{"atif_sayisi": 3263, "atiflar": ["W121109915", "W1456419604", "W1509335780", "W1519022452", "W1519441411", "W1525154317", "W1529762732", "W1545503281", "W1565303318", "W1570910952", "W1574140047", "W1603755042", "W1604513294", "W1608344832", "W1611789306", "W1854798937", "W1915712652", "W1930693802", "W1931293178", "W1938975553", "W1968879734", "W1974554226", "W1975642651", "W1978519770", "W1979043845", "W1984951301", "W1989021341", "W1995074694", "W1999182913", "W2000413909", "W2005536723", "W2012169750", "W2017499074", "W2025828050", "W2036803704", "W2037239040", "W2038515975", "W2045956897", "W2050759207", "W2052651841", "W2057015841", "W2069169311", "W2074571771", "W2090940799", "W2092045274", "W2104008347", "W2105490477", "W2110932975", "W2138078972", "W2154668531", "W2162784992", "W2170202796", "W2198367915", "W2260076009", "W2380139995", "W2415639145", "W4231876369"], "baslik": "A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002).", "doi": "https://doi.org/10.1016/s0021-9258(17)37680-9", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Benzopyran", "Phosphatidylinositol", "LY294002", "Chemistry", "Kinase", "Stereochemistry"], "kimlik": "W1529396499", "ozet": "Phosphatidylinositol (PtdIns) 3-kinase is an enzyme implicated in growth factor signal transduction by associating with receptor and nonreceptor tyrosine kinases, including the platelet-derived growth factor receptor. Inhibitors of PtdIns 3-kinase could potentially give a better understanding of the function and regulatory mechanisms of the enzyme. Quercetin, a naturally occurring bioflavinoid, was previously shown to inhibit PtdIns 3-kinase with an IC50 of 1.3 microgram/ml (3.8 microM); inhibition appeared to be directed at the ATP-binding site of the kinase. Analogs of quercetin were investigated as PtdIns 3-kinase inhibitors, with the most potent ones exhibiting IC50 values in the range of 1.7-8.4 micrograms/ml. In contrast, genistein, a potent tyrosine kinase inhibitor of the isoflavone class, did not inhibit PtdIns 3-kinase significantly (IC50 > 30 micrograms/ml). Since quercetin has also been shown to inhibit other PtdIns and protein kinases, other chromones were evaluated as inhibitors of PtdIns 3-kinase without affecting PtdIns 4-kinase or selected protein kinases. One such compound, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (also known as 2-(4-morpholinyl)-8-phenylchromone, LY294002), completely and specifically abolished PtdIns 3-kinase activity (IC50 = 0.43 microgram/ml; 1.40 microM) but did not inhibit PtdIns 4-kinase or tested protein and lipid kinases. Analogs of LY294002 demonstrated a very selective structure-activity relationship, with slight changes in structure causing marked decreases in inhibition. LY294002 was shown to completely abolish PtdIns 3-kinase activity in fMet-Leu-Phe-stimulated human neutrophils, as well as inhibit proliferation of smooth muscle cells in cultured rabbit aortic segments. Since PtdIns 3-kinase appears to be centrally involved with growth factor signal transduction, the development of specific inhibitors against the kinase may be beneficial in the treatment of proliferative diseases as well as in elucidating the biological role of the kinase in cellular proliferation and growth factor response.", "tam_metin_adresi": "https://doi.org/10.1016/s0021-9258(17)37680-9", "yayinci": "Elsevier BV", "yazarlar": ["Chris J. Vlahos", "William F. Matter", "K. Y. Hui", "Raymond F. Brown"], "yil": 1994}
{"doi": "https://doi.org/10.1016/s0969-2126(99)80086-0", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2019293169"}
{"doi": "https://doi.org/10.1016/s1097-2765(00)80357-3", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2088806906"}
{"atif_sayisi": 551, "atiflar": ["W20584588", "W1497648141", "W1564274931", "W1568067102", "W1763097477", "W1976382352", "W1977872674", "W1978068747", "W1979520552", "W1980166683", "W1980768491", "W1980831535", "W1997509253", "W2024606569", "W2040470926", "W2056831005", "W2062205148", "W2070853191", "W2071877809", "W2072858790", "W2083230754", "W2085559812", "W2104324075", "W2142541950", "W2157640845", "W2159979956"], "baslik": "BMS-345541 Is a Highly Selective Inhibitor of IκB Kinase That Binds at an Allosteric Site of the Enzyme and Blocks NF-κB-dependent Transcription in Mice", "doi": "https://doi.org/10.1074/jbc.m209677200", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Allosteric regulation", "Chemistry", "Enzyme", "Transcription (linguistics)", "Transcription factor", "Binding site", "Kinase", "Allosteric enzyme"], "kimlik": "W2122734862", "ozet": "The signal-inducible phosphorylation of serines 32 and 36 of I kappa B alpha is critical in regulating the subsequent ubiquitination and proteolysis of I kappa B alpha, which then releases NF-kappa B to promote gene transcription. The multisubunit I kappa B kinase responsible for this phosphorylation contains two catalytic subunits, termed I kappa B kinase (IKK)-1 and IKK-2. BMS-345541 (4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline) was identified as a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC(50) = 0.3 microm, IKK-1 IC(50) = 4 microm). The compound failed to inhibit a panel of 15 other kinases and selectively inhibited the stimulated phosphorylation of I kappa B alpha in cells (IC(50) = 4 microm) while failing to affect c-Jun and STAT3 phosphorylation, as well as mitogen-activated protein kinase-activated protein kinase 2 activation in cells. Consistent with the role of IKK/NF-kappa B in the regulation of cytokine transcription, BMS-345541 inhibited lipopolysaccharide-stimulated tumor necrosis factor alpha, interleukin-1 beta, interleukin-8, and interleukin-6 in THP-1 cells with IC(50) values in the 1- to 5-microm range. Although a Dixon plot of the inhibition of IKK-2 by BMS-345541 showed a non-linear relationship indicating non-Michaelis-Menten kinetic binding, the use of multiple inhibition analyses indicated that BMS-345541 binds in a mutually exclusive manner with respect to a peptide inhibitor corresponding to amino acids 26-42 of I kappa B alpha with Ser-32 and Ser-36 changed to aspartates and in a non-mutually exclusive manner with respect to ADP. The opposite results were obtained when studying the binding to IKK-1. A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 was also shown to have excellent pharmacokinetics in mice, and peroral administration showed the compound to dose-dependently inhibit the production of serum tumor necrosis factor alpha following intraperitoneal challenge with lipopolysaccharide. Thus, the compound is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models.", "tam_metin_adresi": "https://doi.org/10.1074/jbc.m209677200", "yayinci": "Elsevier BV", "yazarlar": ["James R. Burke", "Mark A. Pattoli", "Kurt R. Gregor", "Patrick Brassil", "John F. MacMaster", "Kim W. McIntyre", "Xiaoxia Yang", "Violetta S. Iotzova", "Wendy Clarke", "Joann Strnad", "Yuping Qiu", "F. Christopher Zusi"], "yil": 2003}
{"atif_sayisi": 763, "atiflar": ["W27838513", "W66967581", "W1659692600", "W1954313480", "W1976421760", "W1995634658", "W2021996848", "W2040264246", "W2045993433", "W2058992264", "W2064047613", "W2087415667", "W2088597803", "W2098287668", "W2114291028", "W2135836172", "W2155977433", "W2189849157", "W2291334052", "W2411428032", "W2413359840", "W4240064739", "W4249359548"], "baslik": "ZD1839, a Selective Oral Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor, Is Well Tolerated and Active in Patients With Solid, Malignant Tumors: Results of a Phase I Trial", "doi": "https://doi.org/10.1200/jco.2002.10.112", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`Lippincott Williams & Wilkins`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "Lippincott Williams & Wilkins"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Medicine", "Tolerability", "Pharmacokinetics", "Rash", "Adverse effect", "Internal medicine", "Gastroenterology", "Pharmacology"], "kimlik": "W2167368130", "ozet": "PURPOSE: To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS: This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS: Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for > or = 6 months. CONCLUSION: ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.", "tam_metin_adresi": null, "yayinci": "Lippincott Williams & Wilkins", "yazarlar": ["Malcolm Ranson", "Lisa A. Hammond", "D. K. Ferry", "Mark G. Kris", "Andrew B. Tullo", "Philip I. Murray", "V. A. Miller", "Steve Averbuch", "Judy Ochs", "Charles Morris", "A. Feyereislova", "Helen Swaisland"], "yil": 2002}
{"atif_sayisi": 636, "atiflar": ["W1485875137", "W1511853133", "W1518520618", "W1868766650", "W1875554126", "W1964005024", "W1978139448", "W1983622721", "W1999569236", "W1999966467", "W2000292756", "W2001658518", "W2014148719", "W2055865770", "W2073212944", "W2082320957", "W2085904846", "W2089961321", "W2097373408", "W2098482284", "W2103685844", "W2104311705", "W2106695112", "W2112380414", "W2123334268", "W2123769946", "W2126275851", "W2130105793", "W2133619269", "W2135743455", "W2139511378", "W2145835533", "W2149456801", "W2157769714", "W2157868564", "W2159241628", "W2162352067", "W2166156136", "W2168438265", "W2170779902", "W2171715330", "W2184879005", "W2249449600", "W2266575112", "W2282440226", "W2284996855", "W2517521286", "W2589250791", "W2804842145"], "baslik": "Nonclinical Antiangiogenesis and Antitumor Activities of Axitinib (AG-013736), an Oral, Potent, and Selective Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinases 1, 2, 3", "doi": "https://doi.org/10.1158/1078-0432.ccr-08-0652", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Axitinib", "Pharmacology", "Tyrosine-kinase inhibitor", "Vascular endothelial growth factor", "Tyrosine kinase", "Receptor tyrosine kinase", "Medicine", "Cancer research"], "kimlik": "W2106932520", "ozet": "PURPOSE: Axitinib (AG-013736) is a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases 1 to 3 that is in clinical development for the treatment of solid tumors. We provide a comprehensive description of its in vitro characteristics and activities, in vivo antiangiogenesis, and antitumor efficacy and translational pharmacology data. EXPERIMENTAL DESIGN: The potency, kinase selectivity, pharmacologic activity, and antitumor efficacy of axitinib were assessed in various nonclinical models. RESULTS: Axitinib inhibits cellular autophosphorylation of VEGF receptors (VEGFR) with picomolar IC(50) values. Counterscreening across multiple kinase and protein panels shows it is selective for VEGFRs. Axitinib blocks VEGF-mediated endothelial cell survival, tube formation, and downstream signaling through endothelial nitric oxide synthase, Akt and extracellular signal-regulated kinase. Following twice daily oral administration, axitinib produces consistent and dose-dependent antitumor efficacy that is associated with blocking VEGFR-2 phosphorylation, vascular permeability, angiogenesis, and concomitant induction of tumor cell apoptosis. Axitinib in combination with chemotherapeutic or targeted agents enhances antitumor efficacy in many tumor models compared with single agent alone. Dose scheduling studies in a human pancreatic tumor xenograft model show that simultaneous administration of axitinib and gemcitabine without prolonged dose interruption or truncation of axitinib produces the greatest antitumor efficacy. The efficacious drug concentrations predicted in nonclinical studies are consistent with the range achieved in the clinic. Although axitinib inhibits platelet-derived growth factor receptors and KIT with nanomolar in vitro potencies, based on pharmacokinetic/pharmacodynamic analysis, axitinib acts primarily as a VEGFR tyrosine kinase inhibitor at the current clinical exposure. CONCLUSIONS: The selectivity, potency for VEGFRs, and robust nonclinical activity may afford broad opportunities for axitinib to improve cancer therapy.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Dana D. Hu‐Lowe", "Helen Y. Zou", "Maren L. Grazzini", "Max Hallin", "Grant Wickman", "Karin Amundson", "Jeffrey H. Chen", "David A. Rewolinski", "Shinji Yamazaki", "Xinglin Wu", "Michele McTigue", "Brion W. Murray"], "yil": 2008}
{"atif_sayisi": 646, "atiflar": ["W26155307", "W1263601218", "W1432640003", "W1559314541", "W1804903119", "W1837651204", "W1913061990", "W1945415917", "W1974165456", "W1977380140", "W1991958278", "W2001453148", "W2010174111", "W2052815740", "W2063893852", "W2064047613", "W2074070420", "W2101276992", "W2116150263", "W2118146357", "W2129941826", "W2133138712", "W2134582008", "W2142760959", "W2151220251", "W2159506251", "W2163402367", "W2319962899", "W2324677651"], "baslik": "Inhibition of growth factor production and angiogenesis in human cancer cells by ZD1839 (Iressa), a selective epidermal growth factor receptor tyrosine kinase inhibitor.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Autocrine signalling", "Paracrine signalling", "Cancer research", "Angiogenesis", "Basic fibroblast growth factor", "Vascular endothelial growth factor", "Internal medicine", "Growth factor receptor inhibitor"], "kimlik": "W2155977433", "ozet": "The transforming growth factor-alpha/epidermal growth factor receptor (TGF-alpha-EGFR) autocrine pathway, which is involved in the development and the progression of human epithelial cancers, controls, in part, the production of angiogenic factors. These angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are secreted by cancer cells to stimulate normal endothelial cell growth through paracrine mechanisms. ZD1839 (Iressa) is a p.o.-active, selective EGFR-tyrosine kinase inhibitor (TKI) in clinical trials in cancer patients. In this study, we evaluated the antiangiogenic and antitumor activity of ZD1839 in human colon (GEO, SW480, and CaCo2), breast (ZR-75-1 and MCF-7 ADR), ovarian (OVCAR-3), and gastric (KATO III and N87) cancer cells that coexpress TGF-alpha and EGFR. ZD1839 treatment determined a dose- and time-dependent growth inhibition accompanied by the decrease of VEGF, bFGF and TGF-alpha production in vitro. Treatment of immunodeficient mice bearing well-established, palpable GEO xenografts with ZD1839 determined a cytostatic dose-dependent tumor growth inhibition. Immunohistochemical analysis of GEO tumor xenografts after ZD1839 treatment revealed a significant dose-dependent reduction of TGF-alpha, bFGF, and VEGF expression in cancer cells and of neoangiogenesis, as determined by microvessel count. Furthermore, the antitumor activity of ZD1839 was potentiated in combination with the cytotoxic drug paclitaxel in GEO tumor xenografts. Tumor regression was observed in all mice after treatment with ZD1839 plus paclitaxel, and it was accompanied by a significant potentiation in inhibition of TGF-alpha, VEGF, and bFGF expression with a few or no microvessels. Furthermore, 6 of 16 mice bearing well-established, palpable GEO xenografts had no histological evidence of GEO tumors at the end of treatment with ZD1839 plus paclitaxel. These results demonstrate that the antitumor effect of ZD1839 is accompanied by inhibition in the production of autocrine and paracrine growth factors that sustain autonomous local growth and facilitate angiogenesis, and that this effect can be potentiated by the combined treatment with certain cytotoxic drugs, such as paclitaxel.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Fortunato Ciardiello", "Rosa Caputo", "Roberto Bianco", "Vincenzo Damiano", "Gabriella Fontanini", "Sabina Cuccato", "Sabino De Placido", "A R Bianco", "Giampaolo Tortora"], "yil": 2001}
{"atif_sayisi": 383, "atiflar": ["W199978508", "W1493453469", "W1517868493", "W1523413388", "W1540012817", "W1608739560", "W1801742181", "W1829587101", "W1976225087", "W1977565331", "W1985976240", "W1986924929", "W1992348202", "W1993345471", "W2000875208", "W2011960630", "W2015521668", "W2019216438", "W2033867789", "W2038413203", "W2053305824", "W2057079741", "W2071549499", "W2082622773", "W2089103836", "W2091097441", "W2096843911", "W2131823788", "W2140395974", "W2144648936", "W2154066874", "W2163690533", "W2237058775", "W2250687747", "W2312332840", "W2316021978", "W2339207738", "W2344463338", "W2345476533", "W2346748817", "W2558640761", "W2561449166", "W2562706714", "W2587387808", "W2979348411", "W4210733855", "W6608189594"], "baslik": "Acalabrutinib (ACP-196): A Covalent Bruton Tyrosine Kinase Inhibitor with a Differentiated Selectivity and In Vivo Potency Profile", "doi": "https://doi.org/10.1124/jpet.117.242909", "gerekce": "`cc-by-nc` — NC: ticari kullanım yasak", "gerekce_kodu": "kisitli_acik_lisans", "gerekce_param": {"kisit": "NC: ticari kullanım yasak", "lisans": "cc-by-nc"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Bruton's tyrosine kinase", "Chemistry", "Ibrutinib", "In vivo", "Pharmacology", "Tyrosine kinase", "Potency", "Peripheral blood mononuclear cell"], "kimlik": "W2750906538", "ozet": "Several small-molecule Bruton tyrosine kinase (BTK) inhibitors are in development for B cell malignancies and autoimmune disorders, each characterized by distinct potency and selectivity patterns. Herein we describe the pharmacologic characterization of BTK inhibitor acalabrutinib [compound 1, ACP-196 (4-[8-amino-3-[(2S)-1-but-2-ynoylpyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-N-(2-pyridyl)benzamide)]. Acalabrutinib possesses a reactive butynamide group that binds covalently to Cys481 in BTK. Relative to the other BTK inhibitors described here, the reduced intrinsic reactivity of acalabrutinib helps to limit inhibition of off-target kinases having cysteine-mediated covalent binding potential. Acalabrutinib demonstrated higher biochemical and cellular selectivity than ibrutinib and spebrutinib (compounds 2 and 3, respectively). Importantly, off-target kinases, such as epidermal growth factor receptor (EGFR) and interleukin 2-inducible T cell kinase (ITK), were not inhibited. Determination of the inhibitory potential of anti-immunoglobulin M–induced CD69 expression in human peripheral blood mononuclear cells and whole blood demonstrated that acalabrutinib is a potent functional BTK inhibitor. In vivo evaluation in mice revealed that acalabrutinib is more potent than ibrutinib and spebrutinib. Preclinical and clinical studies showed that the level and duration of BTK occupancy correlates with in vivo efficacy. Evaluation of the pharmacokinetic properties of acalabrutinib in healthy adult volunteers demonstrated rapid absorption and fast elimination. In these healthy individuals, a single oral dose of 100 mg showed approximately 99% median target coverage at 3 and 12 hours and around 90% at 24 hours in peripheral B cells. In conclusion, acalabrutinib is a BTK inhibitor with key pharmacologic differentiators versus ibrutinib and spebrutinib and is currently being evaluated in clinical trials.", "tam_metin_adresi": null, "yayinci": "American Society for Pharmacology and Experimental Therapeutics", "yazarlar": ["Tjeerd Barf", "Todd Covey", "Raquel Izumi", "Bas van de Kar", "Michael Gulrajani", "Bart van Lith", "Maaike van Hoek", "Edwin de Zwart", "Diana Mittag", "Dennis Demont", "Saskia Verkaik", "Fanny Krantz"], "yil": 2017}
{"atif_sayisi": 359, "atiflar": ["W248383993", "W1506889194", "W1690318541", "W1964544952", "W1972429976", "W1976225087", "W1979816280", "W1982114584", "W1986924929", "W2002207761", "W2010993054", "W2019216438", "W2025703773", "W2031520822", "W2033867789", "W2053305824", "W2068473321", "W2069928143", "W2071549499", "W2071776905", "W2093522627", "W2113764179", "W2144081223", "W2154066874", "W2154197653", "W2155827443", "W2163341755", "W2163690533", "W2166169438", "W2166422945", "W2171594021", "W2237058775", "W2316021978", "W2338241669", "W2340425144", "W2588396597", "W2599467614", "W2622009965", "W2770172979", "W2884870468", "W2924170743", "W4248872320"], "baslik": "Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase", "doi": "https://doi.org/10.1021/acs.jmedchem.9b00687", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Bruton's tyrosine kinase", "Chemistry", "ADME", "In vivo", "Tyrosine kinase", "Pharmacology", "Kinase", "In vitro"], "kimlik": "W2972482801", "ozet": "Aberrant activation of Bruton’s tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 ( 31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Yunhang Guo", "Ye Liu", "Nan Hu", "Desheng Yu", "Changyou Zhou", "Gongyin Shi", "Bo Zhang", "Wei Min", "Junhua Liu", "Lusong Luo", "Zhiyu Tang", "Huipeng Song"], "yil": 2019}
{"doi": "https://doi.org/10.1038/ncomms1090", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2168175722"}
{"doi": "https://doi.org/10.1016/s0006-291x(84)80362-9", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2085909636"}
{"doi": "https://doi.org/10.1182/blood-2017-09-808808", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2794058157"}
{"atif_sayisi": 424, "atiflar": ["W1561013854", "W1562372296", "W1563031684", "W1575628845", "W1886694278", "W1989203819", "W1989627660", "W2031469256", "W2041896692", "W2053073281", "W2065919583", "W2075395967", "W2088281838", "W2114189030", "W2137772140", "W2140439371", "W2147114673", "W2152679288", "W2156719646", "W2167630501", "W4249991987"], "baslik": "Akt/Protein Kinase B Signaling Inhibitor-2, a Selective Small Molecule Inhibitor of Akt Signaling with Antitumor Activity in Cancer Cells Overexpressing Akt", "doi": "https://doi.org/10.1158/0008-5472.can-04-0343", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Protein kinase B", "Cancer research", "PI3K/AKT/mTOR pathway", "Kinase", "PTEN", "Signal transduction", "Cell biology", "AKT1"], "kimlik": "W2167368929", "ozet": "Accumulated studies have shown that activation of the Akt pathway plays a pivotal role in malignant transformation and chemoresistance by inducing cell survival, growth, migration, and angiogenesis. Therefore, Akt is believed to be a critical target for cancer intervention. Here, we report the discovery of a small molecule Akt pathway inhibitor, Akt/protein kinase B signaling inhibitor-2 (API-2), by screening the National Cancer Institute Diversity Set. API-2 suppressed the kinase activity and phosphorylation level of Akt. The inhibition of Akt kinase resulted in suppression of cell growth and induction of apoptosis in human cancer cells that harbor constitutively activated Akt due to overexpression of Akt or other genetic alterations such as PTEN mutation. API-2 is highly selective for Akt and does not inhibit the activation of phosphatidylinositol 3'-kinase, phosphoinositide-dependent kinase-1, protein kinase C, serum- and glucocorticoid-inducible kinase, protein kinase A, signal transducer and activators of transcription 3, extracellular signal-regulated kinase-1/2, or c-Jun NH(2)-terminal kinase. Furthermore, API-2 potently inhibited tumor growth in nude mice of human cancer cells in which Akt is aberrantly expressed/activated but not of those cancer cells in which it is not. These findings provide strong evidence for pharmacologically targeting Akt for anticancer drug discovery.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Lin Yang", "Han C. Dan", "Mei Sun", "Qiyuan Liu", "Xia-meng Sun", "Richard I. Feldman", "Andrew D. Hamilton", "Mark A. Polokoff", "Santo V. Nicosia", "Meenhard Herlyn", "Saı̈d M. Sebti", "Jin Q. Cheng"], "yil": 2004}
{"atif_sayisi": 221, "atiflar": [], "baslik": "Butyrolactone I, a selective inhibitor of cdk2 and cdc2 kinase.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Cyclin-dependent kinase 2", "Cyclin-dependent kinase 1", "Biology", "Cyclin-dependent kinase 9", "MAP kinase kinase kinase", "Cyclin-dependent kinase 4", "Mitogen-activated protein kinase kinase", "MAP2K7"], "kimlik": "W2399621249", "ozet": "We screened cdc2 kinase inhibitors from cultured mediums of micro organisms using purified mouse cyclin B-cdc2 kinase and a specific substrate peptide for cdc2 kinase. A selective inhibitor of cdc2 kinase was isolated from the cultured medium of Aspergillus species F-25799, and identified as butyrolactone I. Butyrolactone I inhibited cdc2 and cdk2 kinases but it had little effect on mitogen-activated protein kinase, protein kinase C, cyclic-AMP dependent kinase, casein kinase II, casein kinase I or epidermal growth factor-receptor tyrosine kinase. Its inhibitory effect was found to be due to competition with ATP. Butyrolactone I selectively inhibited the H1 histone phosphorylation in nuclear extracts. It also inhibited the phosphorylation of the product of retinoblastoma susceptibility gene in nuclear extracts and intact cells. Thus butyrolactone I should be very useful for elucidating the function of cdc2 and cdk2 kinases in cell cycle regulation.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Masatoshi Kitagawa", "Takayoshi Okabe", "H Ogino", "Hisanori Matsumoto", "Ikuko Suzuki‐Takahashi", "Tadayoshi Kokubo", "Hideaki Higashi", "S Saitoh", "Yoichi Taya", "Hideyo Yasuda"], "yil": 1993}
{"doi": "https://doi.org/10.1016/0014-5793(94)80232-7", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2086046451"}
{"atif_sayisi": 3267, "atiflar": ["W31151557", "W61379093", "W63697704", "W81266651", "W91182734", "W129012576", "W139338291", "W143753117", "W169454248", "W196685199", "W200461798", "W257159349", "W273460782", "W1497143324", "W1501631032", "W1545424811", "W1552964273", "W1596456096", "W1610470214", "W1834547194", "W1845790496", "W1847864430", "W1854548319", "W1868808920", "W1965080968", "W1966797025", "W1971245466", "W1971512164", "W1974391793", "W1975324295", "W1976875150", "W1977299280", "W1979669293", "W1980720313", "W1981391513", "W1982245444", "W1982622947", "W1982768428", "W1983348452", "W1983971803", "W1986179131", "W1988661251", "W1988756673", "W1988762859", "W1989936068", "W1990743609", "W1990925999", "W1994066190", "W1996413533", "W1997012271", "W1997073961", "W1997643531", "W1999876280", "W2003282728", "W2003907692", "W2005222967", "W2005677707", "W2005941837", "W2007255413", "W2007267903", "W2007772649", "W2007993419", "W2008693579", "W2009573109", "W2010493387", "W2012293213", "W2013330927", "W2015519364", "W2017091696", "W2017599618", "W2017689200", "W2021326683", "W2022329296", "W2022502588", "W2024849327", "W2027376766", "W2027558915", "W2028361915", "W2030231219", "W2030283142", "W2032428064", "W2033156691", "W2036817346", "W2038407368", "W2040687166", "W2041206676", "W2043311475", "W2046577405", "W2047953965", "W2048721919", "W2048743150", "W2051481282", "W2051541258", "W2051618204", "W2052651806", "W2055085859", "W2055349083", "W2058668641", "W2060941065", "W2061645351", "W2063367127", "W2066848701", "W2069533174", "W2070061120", "W2073691035", "W2074114480", "W2076273397", "W2078427074", "W2078581194", "W2078596153", "W2078690152", "W2078718449", "W2079384901", "W2081282586", "W2081290278", "W2082178421", "W2086773265", "W2088831705", "W2089218510", "W2090303261", "W2092104789", "W2092543937", "W2094585804", "W2095690095", "W2095711408", "W2097043033", "W2098412103", "W2108172661", "W2112555367", "W2123449896", "W2125297918", "W2125555976", "W2128739161", "W2133697463", "W2134331780", "W2135535670", "W2138103542", "W2144942522", "W2147242002", "W2147817953", "W2152028923", "W2153488262", "W2157721629", "W2161378573", "W2163663331", "W2164145069", "W2167198441", "W2170331239", "W2171367003", "W2289050278", "W2396288039", "W2417531610", "W4231271646", "W4246253484"], "baslik": "Inhibitors of mammalian G1 cyclin-dependent kinases.", "doi": "https://doi.org/10.1101/gad.9.10.1149", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Biology", "Kinase", "Cyclin-dependent kinase", "Cell biology", "Protein-Serine-Threonine Kinases", "Cyclin", "Cell cycle", "Cancer research"], "kimlik": "W2015066175", "ozet": "C J Sherr and J M Roberts Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38104, USA.", "tam_metin_adresi": null, "yayinci": "Cold Spring Harbor Laboratory Press", "yazarlar": ["Charles J. Sherr", "Joanna Roberts"], "yil": 1995}
{"doi": "https://doi.org/10.1182/blood-2007-03-080689", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2057718276"}
{"doi": "https://doi.org/10.4161/cc.3.4.772", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Taylor & Francis` (P4310320547) `Informa` grubuna ait: Taylor & Francis ana şirketi · 157K eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Taylor & Francis` (P4310320547) `Informa` grubuna ait: Taylor & Francis ana şirketi · 157K eser"}, "izin": "ENGELLI", "kimlik": "W2037798660"}
{"atif_sayisi": 40, "atiflar": ["W1543963511", "W1964837805", "W1967194754", "W1974903851", "W1979767649", "W1983782238", "W1984364760", "W1988212011", "W1993438476", "W1993976538", "W1995808589", "W1998028009", "W2001097406", "W2006436808", "W2014582878", "W2015015957", "W2016602387", "W2019523557", "W2020257412", "W2020450593", "W2030205108", "W2037947892", "W2039782788", "W2045192688", "W2052201526", "W2053106209", "W2065283382", "W2072582769", "W2086286404", "W2093615982", "W2096993465", "W2100772783", "W2108042184", "W2108285390", "W2124955716", "W2129747161", "W2138675533", "W2142702787", "W2152265294", "W2158315886", "W2169363650", "W2259381440", "W2288765870", "W2329648702", "W2339666810", "W2416046665", "W2575507470", "W2744129621", "W2750674172", "W2920332650", "W4236708157"], "baslik": "Computational analysis of kinase inhibitor selectivity using structural knowledge", "doi": "https://doi.org/10.1093/bioinformatics/bty582", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`Oxford University Press`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "Oxford University Press"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Computer science", "Kinase", "Selectivity", "Computational biology"], "kimlik": "W2869298098", "ozet": "Motivation: Kinases play a significant role in diverse disease signaling pathways and understanding kinase inhibitor selectivity, the tendency of drugs to bind to off-targets, remains a top priority for kinase inhibitor design and clinical safety assessment. Traditional approaches for kinase selectivity analysis using biochemical activity and binding assays are useful but can be costly and are often limited by the kinases that are available. On the other hand, current computational kinase selectivity prediction methods are computational intensive and can rarely achieve sufficient accuracy for large-scale kinome wide inhibitor selectivity profiling. Results: Here, we present a KinomeFEATURE database for kinase binding site similarity search by comparing protein microenvironments characterized using diverse physiochemical descriptors. Initial selectivity prediction of 15 known kinase inhibitors achieved an >90% accuracy and demonstrated improved performance in comparison to commonly used kinase inhibitor selectivity prediction methods. Additional kinase ATP binding site similarity assessment (120 binding sites) identified 55 kinases with significant promiscuity and revealed unexpected inhibitor cross-activities between PKR and FGFR2 kinases. Kinome-wide selectivity profiling of 11 kinase drug candidates predicted novel as well as experimentally validated off-targets and suggested structural mechanisms of kinase cross-activities. Our study demonstrated potential utilities of our approach for large-scale kinase inhibitor selectivity profiling that could contribute to kinase drug development and safety assessment. Availability and implementation: The KinomeFEATURE database and the associated scripts for performing kinase pocket similarity search can be downloaded from the Stanford SimTK website (https://simtk.org/projects/kdb). Supplementary information: Supplementary data are available at Bioinformatics online.", "tam_metin_adresi": null, "yayinci": "Oxford University Press", "yazarlar": ["Yu‐Chen Lo", "Tianyun Liu", "Kari M. Morrissey", "Satoko Kakiuchi-Kiyota", "Adam R. Johnson", "Fabio Broccatelli", "Yu Zhong", "Amita Joshi", "Russ B. Altman"], "yil": 2018}
{"doi": "https://doi.org/10.1016/j.bmcl.2004.09.060", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2178647298"}
{"doi": "https://doi.org/10.1016/s0960-894x(96)00601-4", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2021497478"}
{"atif_sayisi": 51, "atiflar": ["W1482218984", "W1970264868", "W1978686683", "W1998071315", "W2001097406", "W2003973314", "W2014582878", "W2017975014", "W2021528276", "W2030205108", "W2070269476", "W2081573377", "W2086476425", "W2087023176", "W2091818624", "W2100772783", "W2117814548", "W2130105793", "W2135129680", "W2138072853", "W2525012249"], "baslik": "Analysis of Kinase Inhibitor Selectivity using a Thermodynamics-Based Partition Index", "doi": "https://doi.org/10.1021/jm100301x", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinome", "Selectivity", "Chemistry", "Topological index", "Kinase", "Partition coefficient", "Partition (number theory)", "Combinatorial chemistry"], "kimlik": "W2025156367", "ozet": "In the quest for safe, efficacious kinase inhibitors as drugs, selectivity is often assessed early using kinase profiling panels. Here we present a selectivity index based on thermodynamics principles that can help in analysis of the resulting data. The \"partition\" selectivity index is easy to calculate and is applicable in certain situations where other widely used indices are not. It is uniquely useful in analysis of small, focused selectivity panel data frequently encountered in medicinal chemistry hit-to-lead and lead optimization. For larger \"kinome\" panels, the partition index allows assessment of selectivity relative to a kinase or multiple kinases of interest.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Alan C. Cheng", "John Eksterowicz", "Stephanie Geuns-Meyer", "Yaxiong Sun"], "yil": 2010}
{"atif_sayisi": 56, "atiflar": ["W1490860457", "W1845618662", "W1964758803", "W1974030600", "W1976499671", "W1980673831", "W1989793475", "W1995152253", "W1996420136", "W2001368885", "W2003217611", "W2009987871", "W2011905613", "W2012238745", "W2014433873", "W2016602387", "W2017829285", "W2020450593", "W2021019774", "W2025820706", "W2027408247", "W2027539373", "W2032222348", "W2033989981", "W2035460800", "W2035672721", "W2037652551", "W2043760657", "W2049885874", "W2050333027", "W2050774715", "W2054478209", "W2067174909", "W2068535486", "W2073714240", "W2077534726", "W2090004346", "W2102376488", "W2106140689", "W2107803322", "W2112154906", "W2120273997", "W2131174104", "W2131756681", "W2132262459", "W2137601120", "W2138072853", "W2146928870", "W2150981663", "W2156507631", "W2156973770", "W2161504119", "W2162166182", "W2327533467"], "baslik": "Computational Study of Gleevec and G6G Reveals Molecular Determinants of Kinase Inhibitor Selectivity", "doi": "https://doi.org/10.1021/ja504146x", "gerekce": "telifli görünüyor (lisans=`other-oa`, yayıncı=`American Chemical Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "other-oa", "yayinci": "American Chemical Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Chemistry", "Selectivity", "Kinase", "Enzyme inhibitor"], "kimlik": "W2083116013", "ozet": "Gleevec is a potent inhibitor of Abl tyrosine kinase but not of the highly homologous c-Src kinase. Because the ligand binds to an inactive form of the protein in which an Asp-Phe-Gly structural motif along the activation loop adopts a so-called DFG-out conformation, it was suggested that binding specificity was controlled by a \"conformational selection\" mechanism. In this context, the binding affinity displayed by the kinase inhibitor G6G poses an intriguing challenge. Although it possesses a chemical core very similar to that of Gleevec, G6G is a potent inhibitor of both Abl and c-Src kinases. Both inhibitors bind to the DFG-out conformation of the kinases, which seems to be in contradiction with the conformational selection mechanism. To address this issue and display the hidden thermodynamic contributions affecting the binding selectivity, molecular dynamics free energy simulations with explicit solvent molecules were carried out. Relative to Gleevec, G6G forms highly favorable van der Waals dispersive interactions upon binding to the kinases via its triazine functional group, which is considerably larger than the corresponding pyridine moiety in Gleevec. Upon binding of G6G to c-Src, these interactions offset the unfavorable free energy cost of the DFG-out conformation. When binding to Abl, however, G6G experiences an unfavorable free energy penalty due to steric clashes with the phosphate-binding loop, yielding an overall binding affinity that is similar to that of Gleevec. Such steric clashes are absent when G6G binds to c-Src, due to the extended conformation of the phosphate-binding loop.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Yen-lin Lin", "Yilin Meng", "Lei Huang", "Benoı̂t Roux"], "yil": 2014}
{"atif_sayisi": 214, "atiflar": ["W187187964", "W1584889342", "W1986259767", "W2009069712", "W2022622009", "W2030205108", "W2030759806", "W2034745954", "W2038851107", "W2050422354", "W2058735345", "W2060854787", "W2063181387", "W2089258979", "W2091677235", "W2095326842", "W2102781162", "W2111121646", "W2115902508", "W2141138459", "W2144980016", "W2162653488", "W2169414689", "W2313959235", "W4235978374", "W4247904703"], "baslik": "Gini Coefficient: A New Way To Express Selectivity of Kinase Inhibitors against a Family of Kinases", "doi": "https://doi.org/10.1021/jm070562u", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Chemical Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Chemical Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Chemistry", "Selectivity", "Staurosporine", "Biochemistry"], "kimlik": "W2070269476", "ozet": "A novel application of the Gini coefficient for expressing selectivity of kinase inhibitors against a panel of kinases is proposed. This has been illustrated using single-point inhibition data for 40 commercially available kinase inhibitors screened against 85 kinases. Nonselective inhibitors are characterized by Gini values close to zero (Staurosporine, Gini 0.150). Highly selective compounds exhibit Gini values close to 1 (PD184352 Gini 0.905). The relative selectivity of inhibitors does not depend on the ATP concentration.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Piotr Graczyk"], "yil": 2007}
{"doi": "https://doi.org/10.1046/j.1471-4159.2001.t01-1-00251.x", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2012868552"}
{"atif_sayisi": 487, "atiflar": ["W1967405376", "W1985229759", "W1992563018", "W2013112408", "W2013739293", "W2016710415", "W2019573100", "W2029353164", "W2043696829", "W2048142144", "W2049274590", "W2064698668", "W2070241543", "W2073140732", "W2082735583", "W2087352606", "W2103894337", "W2110835998", "W2120718661", "W2125730396", "W2127101185", "W2137390717", "W2139236349", "W2141393790", "W2146404049", "W2150501295", "W2153764234", "W2161821474", "W2329648702", "W2400986674", "W4322701878"], "baslik": "Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752", "doi": "https://doi.org/10.1073/pnas.0508776103", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Biology", "Cancer research", "Cancer", "Receptor tyrosine kinase", "Tyrosine kinase", "Gene duplication", "Population", "Cancer cell"], "kimlik": "W2013678879", "ozet": "The success of molecular targeted therapy in cancer may depend on the selection of appropriate tumor types whose survival depends on the drug target, so-called \"oncogene addiction.\" Preclinical approaches to defining drug-responsive subsets are needed if initial clinical trials are to be directed at the most susceptible patient population. Here, we show that gastric cancer cells with high-level stable chromosomal amplification of the growth factor receptor MET are extraordinarily susceptible to the selective inhibitor PHA-665752. Although MET activation has primarily been linked with tumor cell migration and invasiveness, the amplified wild-type MET in these cells is constitutively activated, and its continued signaling is required for cell survival. Treatment with PHA-665752 triggers massive apoptosis in 5 of 5 gastric cancer cell lines with MET amplification but in 0 of 12 without increased gene copy numbers (P = 0.00016). MET amplification may thus identify a subset of epithelial cancers that are uniquely sensitive to disruption of this pathway and define a patient group that is appropriate for clinical trials of targeted therapy using MET inhibitors.", "tam_metin_adresi": null, "yayinci": "National Academy of Sciences", "yazarlar": ["Gromoslaw A. Smolen", "Raffaella Sordella", "Beth Muir", "Gayatry Mohapatra", "Anne Barmettler", "Heidi Archibald", "Woo Jae Kim", "Ross A. Okimoto", "Daphne W. Bell", "Dennis C. Sgroi", "James G. Christensen", "Jeffrey Settleman"], "yil": 2006}
{"atif_sayisi": 358, "atiflar": ["W1965329315", "W1976526593", "W1998971866", "W2005216767", "W2013678879", "W2034048944", "W2049171090", "W2077224394", "W2080686146", "W2103894337", "W2105453387", "W2120365528", "W2121389354", "W2142739240", "W2148783573", "W2150926065", "W2163188200", "W2165119042", "W2167198299", "W2168996492"], "baslik": "Identification of genotype-correlated sensitivity to selective kinase inhibitors by using high-throughput tumor cell line profiling", "doi": "https://doi.org/10.1073/pnas.0707498104", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "Biology", "Cell culture", "Cancer research", "Genotype", "Cell", "Genetics"], "kimlik": "W2008345619", "ozet": "Kinase inhibitors constitute an important new class of cancer drugs, whose selective efficacy is largely determined by underlying tumor cell genetics. We established a high-throughput platform to profile 500 cell lines derived from diverse epithelial cancers for sensitivity to 14 kinase inhibitors. Most inhibitors were ineffective against unselected cell lines but exhibited dramatic cell killing of small nonoverlapping subsets. Cells with exquisite sensitivity to EGFR, HER2, MET, or BRAF kinase inhibitors were marked by activating mutations or amplification of the drug target. Although most cell lines recapitulated known tumor-associated genotypes, the screen revealed low-frequency drug-sensitizing genotypes in tumor types not previously associated with drug susceptibility. Furthermore, comparing drugs thought to target the same kinase revealed striking differences, predictive of clinical efficacy. Genetically defined cancer subsets, irrespective of tissue type, predict response to kinase inhibitors, and provide an important preclinical model to guide early clinical applications of novel targeted inhibitors.", "tam_metin_adresi": null, "yayinci": "National Academy of Sciences", "yazarlar": ["Ultan McDermott", "Sreenath V. Sharma", "Lori Dowell", "Patricia Greninger", "Clara Montagut", "Jennifer Lamb", "Heidi Archibald", "Raul Raudales", "Angela Tam", "Diana Lee", "S. Michael Rothenberg", "Jeffrey G. Supko"], "yil": 2007}
{"atif_sayisi": 388, "atiflar": ["W1501369263", "W1518868828", "W1533874578", "W1966502113", "W1973005880", "W1973466803", "W1974388096", "W1984334393", "W1987404531", "W1991714532", "W1999696701", "W2002507752", "W2004290667", "W2023972740", "W2035175373", "W2036628331", "W2041556575", "W2052415197", "W2055702210", "W2061052988", "W2062570493", "W2062892401", "W2065933401", "W2076507247", "W2088916440", "W2089330962", "W2095621789", "W2099355198", "W2126241200", "W2136556999", "W2136637563", "W2139834613", "W2146217294", "W2151427994", "W2153388221", "W2157029701", "W2157817576", "W2160332942", "W2167955976"], "baslik": "A Selective ε-Protein Kinase C Antagonist Inhibits Protection of Cardiac Myocytes from Hypoxia-induced Cell Death", "doi": "https://doi.org/10.1074/jbc.272.49.30945", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Protein kinase C", "Protein kinase A", "Myocyte", "Ischemic preconditioning", "cGMP-dependent protein kinase", "Mitogen-activated protein kinase kinase", "Kinase", "Cell biology"], "kimlik": "W2023494473", "ozet": "Protein kinase C activation is thought to protect cardiac tissue from subsequent ischemic injury by a process termed preconditioning. The protein kinase C isozyme that mediates preconditioning has not yet been identified. Using a cell culture model of hypoxic preconditioning, we found that cardiac myocyte viability after 9 h of hypoxia was increased by more than 50% over control. Preconditioning activated protein kinase C isozymes as evidenced by translocation from one cell compartment to another as follows: there was a 2.1-fold increase in epsilon-protein kinase C activation, a 2. 8-fold increase in delta-protein kinase C activation, and no increase in betaI-protein kinase C activation. 4beta-Phorbol 12-myristate 13-acetate mimicked hypoxic preconditioning, increasing myocyte survival after prolonged hypoxia by 34% compared with control. We previously identified an epsilon-protein kinase C-selective antagonist, epsilonV1-2 peptide, that inhibits epsilon-protein kinase C translocation and function in cardiac myocytes (Johnson, J. A., Gray, M. O., Chen, C.-H., and Mochly-Rosen, D. (1996) J. Biol. Chem. 271, 24962-24966). epsilonV1-2 peptide abolished hypoxic preconditioning and phorbol ester-mediated cardiac protection. Therefore, preconditioning can be induced in this culture model, and activation of epsilon-protein kinase C is critical for cardiac myocyte protection.", "tam_metin_adresi": "http://www.jbc.org/article/S0021925819896345/pdf", "yayinci": "Elsevier BV", "yazarlar": ["Mary O. Gray", "Joel S. Karliner", "Daria Mochly‐Rosen"], "yil": 1997}
{"doi": "https://doi.org/10.1111/j.1349-7006.2011.01939.x", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Wiley` (P4310320595) `Wiley` grubuna ait: TDM için ayrı lisans gerekiyor · 11,2M eser"}, "izin": "ENGELLI", "kimlik": "W2145092426"}
{"atif_sayisi": 40, "atiflar": [], "baslik": "Clinical significance of Janus Kinase inhibitor selectivity", "doi": "https://doi.org/10.1093/rheumatology/kez002", "gerekce": "açık lisans `cc-by` ticari TDM'e izin veriyor", "gerekce_kodu": "acik_lisans", "gerekce_param": {"lisans": "cc-by"}, "izin": "TAM", "kavramlar": ["Medicine", "Janus kinase", "Janus", "Janus kinase inhibitor", "Kinase", "Internal medicine", "Pharmacology"], "kimlik": "W4239814412", "ozet": "Rheumatology 2019;58:953–62. doi:10.1093/rheumatology/key339 In Table 3, the entry in the ‘DVT/PE’ row, first column ‘Tofacitinib (JAK, JAK3)’ has been replaced with ‘NR’ as it states later in the paper that this is not reported.", "tam_metin_adresi": "https://academic.oup.com/rheumatology/article-pdf/58/6/1122/28697424/kez002.pdf", "yayinci": "Oxford University Press", "yazarlar": ["Ernest Choy"], "yil": 2019}
{"atif_sayisi": 381, "atiflar": ["W23999710", "W114839291", "W1892175722", "W1982542795", "W1995353970", "W1998948060", "W2000441241", "W2007458783", "W2008870093", "W2012077729", "W2019436548", "W2019903301", "W2019931350", "W2029040745", "W2033336766", "W2043509228", "W2046744512", "W2052830222", "W2075610726", "W2097472327", "W2104481491", "W2106880613", "W2116957649", "W2117087517", "W2138647255", "W2141682274", "W2231320375", "W2257779930", "W2258953806", "W2272200366", "W2314067773", "W2315545909", "W2321866796", "W2329371764", "W2336399478", "W2407851381", "W2422726141", "W2547876355", "W2552941407", "W2561041192", "W2562753811", "W2566103724", "W2567535755", "W2611548364", "W2611735159", "W2625769798", "W2749434344", "W2766717228", "W2778514431", "W2781491897", "W2782968698", "W2803339448", "W2806532950", "W2808333862", "W2884090647", "W2887542285", "W2892136519", "W2911145904", "W2945165808", "W2962182289", "W3130650455"], "baslik": "Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165", "doi": "https://doi.org/10.1021/acs.jmedchem.9b00444", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinome", "Allosteric regulation", "Chemistry", "Drug discovery", "Tyrosine kinase 2", "Tyrosine kinase", "Small molecule", "Receptor tyrosine kinase"], "kimlik": "W2956179332", "ozet": "Small molecule JAK inhibitors have emerged as a major therapeutic advancement in treating autoimmune diseases. The discovery of isoform selective JAK inhibitors that traditionally target the catalytically active site of this kinase family has been a formidable challenge. Our strategy to achieve high selectivity for TYK2 relies on targeting the TYK2 pseudokinase (JH2) domain. Herein we report the late stage optimization efforts including a structure-guided design and water displacement strategy that led to the discovery of BMS-986165 ( 11 ) as a high affinity JH2 ligand and potent allosteric inhibitor of TYK2. In addition to unprecedented JAK isoform and kinome selectivity, 11 shows excellent pharmacokinetic properties with minimal profiling liabilities and is efficacious in several murine models of autoimmune disease. On the basis of these findings, 11 appears differentiated from all other reported JAK inhibitors and has been advanced as the first pseudokinase-directed therapeutic in clinical development as an oral treatment for autoimmune diseases.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Stephen T. Wrobleski", "Ryan Moslin", "Shuqun Lin", "Yanlei Zhang", "Steven H. Spergel", "James Kempson", "John S. Tokarski", "Joann Strnad", "Adriana Zupa-Fernandez", "Lihong Cheng", "David J. Shuster", "Kathleen M. Gillooly"], "yil": 2019}
{"doi": "https://doi.org/10.1016/0076-6879(91)01033-x", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Academic Press` (P4310319955) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Academic Press` (P4310319955) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2192686175"}
{"atif_sayisi": 244, "atiflar": ["W100364503", "W1489145507", "W1606090394", "W1688621929", "W1769366348", "W1831026143", "W1970751001", "W1973577899", "W1979147887", "W1979909416", "W1980935526", "W1980969801", "W1984418041", "W1989627660", "W1993852996", "W1999447199", "W2001215449", "W2006932987", "W2017191360", "W2018786910", "W2022114529", "W2029338379", "W2031469256", "W2033783187", "W2041414354", "W2053073281", "W2066457776", "W2068345721", "W2068427129", "W2068581379", "W2073575984", "W2077478539", "W2078359839", "W2078888146", "W2090551359", "W2092353041", "W2096691828", "W2117263216", "W2117905749", "W2119151792", "W2133701720", "W2148785089", "W2148842373", "W2150233389", "W2160115491", "W2161242392", "W2161810908", "W2166336604", "W2167368929", "W2181371279", "W2186305370", "W2339547236", "W2388163742", "W4242061227"], "baslik": "Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo", "doi": "https://doi.org/10.1158/1535-7163.mct-05-0005", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Protein kinase B", "AKT1", "In vivo", "Pharmacology", "Kinase", "Signal transduction", "Cancer research", "AKT2"], "kimlik": "W2112842133", "ozet": "The Akt kinases are central nodes in signal transduction pathways that are important for cellular transformation and tumor progression. We report the development of a series of potent and selective indazole-pyridine based Akt inhibitors. These compounds, exemplified by A-443654 (K(i) = 160 pmol/L versus Akt1), inhibit Akt-dependent signal transduction in cells and in vivo in a dose-responsive manner. In vivo, the Akt inhibitors slow the progression of tumors when used as monotherapy or in combination with paclitaxel or rapamycin. Tumor growth inhibition was observed during the dosing interval, and the tumors regrew when compound administration was ceased. The therapeutic window for these compounds is narrow. Efficacy is achieved at doses approximately 2-fold lower than the maximally tolerated doses. Consistent with data from knockout animals, the Akt inhibitors induce an increase in insulin secretion. They also induce a reactive increase in Akt phosphorylation. Other toxicities observed, including malaise and weight loss, are consistent with abnormalities in glucose metabolism. These data show that direct Akt inhibition may be useful in cancer therapy, but significant metabolic toxicities are likely dose limiting.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Yan Luo", "Alexander R. Shoemaker", "Xuesong Liu", "Keith W. Woods", "Sheela A. Thomas", "Ron de Jong", "Edward K. Han", "Tongmei Li", "Vincent S. Stoll", "Jessica A. Powlas", "Anatol Oleksijew", "Michael J. Mitten"], "yil": 2005}
{"atif_sayisi": 176, "atiflar": ["W260651669", "W1485850033", "W1490418776", "W1510401881", "W1516484156", "W1552274890", "W1858315965", "W1943552404", "W1963869661", "W1965695376", "W1966647991", "W1968071128", "W1971166400", "W1988908019", "W2001848725", "W2014082408", "W2015492609", "W2020724252", "W2023194647", "W2033409103", "W2042794591", "W2054956895", "W2072918638", "W2077047827", "W2078325902", "W2090895449", "W2091735622", "W2095226581", "W2100392335", "W2107015590", "W2132755748", "W2134094496", "W2138963727", "W2139524845", "W2140814882", "W2151504205", "W2156160133", "W2165720262", "W2166056434", "W2166195139", "W2171620774", "W2263837564", "W2318183382"], "baslik": "The Src-selective Kinase Inhibitor PP1 Also Inhibits Kit and Bcr-Abl Tyrosine Kinases", "doi": "https://doi.org/10.1074/jbc.m209321200", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Proto-oncogene tyrosine-protein kinase Src", "Tyrosine kinase", "Kinase", "Tyrosine-kinase inhibitor", "Tyrosine-protein kinase CSK", "ABL", "Chemistry", "SH3 domain"], "kimlik": "W1983879963", "ozet": "4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]- pyrimidine (PP1) was identified as an Src-selective tyrosine kinase inhibitor and has been used extensively to investigate signaling pathways involving Src kinases, including events downstream of the stem cell factor (SCF) receptor c-Kit. While investigating the role of Src kinases in SCF signaling, we found that PP1 completely abrogated the proliferation of M07e cells in response to SCF. PP1 inhibited SCF-induced c-Kit autophosphorylation in intact cells and blocked the activation of mitogen-activated protein kinase and Akt. In vitro kinase assays using immunoprecipitated c-Kit confirmed direct inhibition by PP1. SCF-induced c-Kit phosphorylation was also inhibited by the related inhibitor 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP2) and by STI571 but not by the Src inhibitor SU6656. PP1 inhibited the activity of mutant constitutively active forms of c-Kit (D814V and D814Y) found in mast cell disorders, and triggered apoptosis in the rat basophilic leukemia cell line RBL-2H3 that expresses mutant c-Kit. In addition, PP1 (and PP2) inhibited the in vitro kinase activity and autophosphorylation in whole cells of p210 Bcr-Abl. PP1 reduced the constitutive activation of signal transducer and activators of transcription 5 and mitogen-activated protein kinase and triggered apoptosis in FDCP1 cells expressing Bcr-Abl. These results have implications for the use of PP1 in investigating intracellular signaling and suggest that PP1 or related compounds may be useful in the treatment of malignant diseases associated with dysregulated c-Kit or Abl tyrosine kinase activity.", "tam_metin_adresi": "http://www.jbc.org/article/S0021925819327875/pdf", "yayinci": "Elsevier BV", "yazarlar": ["Louise Tatton", "Gary Morley", "Rajesh Chopra", "Asim Khwaja"], "yil": 2003}
{"atif_sayisi": 322, "atiflar": ["W90465349", "W117902596", "W1538256998", "W1639582946", "W1820115685", "W1909358044", "W1948497307", "W1969732147", "W1974916719", "W1977436845", "W1985995844", "W1997923564", "W2002926055", "W2013678879", "W2018526163", "W2019573100", "W2022052722", "W2040851157", "W2048797151", "W2050983091", "W2051782283", "W2054042846", "W2055787036", "W2077939133", "W2087352606", "W2096844786", "W2102053414", "W2121371052", "W2126890008", "W2127287125", "W2132831751", "W2134442967", "W2136390065", "W2151005088", "W2155167580", "W2155493449", "W2171091535", "W2172339568", "W2189233644", "W2254573112", "W2281242723", "W2328659017", "W2334802216", "W4245967957", "W6632365655", "W6638268772", "W6675087628", "W6678840981", "W6685188281", "W6687105383"], "baslik": "ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity", "doi": "https://doi.org/10.1158/1535-7163.mct-09-1173", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Association for Cancer Research`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Association for Cancer Research"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Receptor tyrosine kinase", "Cancer research", "Tyrosine kinase", "C-Met", "Cell growth", "Oncogene", "Cancer", "Pharmacology"], "kimlik": "W2139073495", "ozet": "The met proto-oncogene is functionally linked with tumorigenesis and metastatic progression. Validation of the receptor tyrosine kinase c-Met as a selective anticancer target has awaited the emergence of selective c-Met inhibitors. Herein, we report ARQ 197 as the first non-ATP-competitive small molecule that selectively targets the c-Met receptor tyrosine kinase. Exposure to ARQ 197 resulted in the inhibition of proliferation of c-Met-expressing cancer cell lines as well as the induction of caspase-dependent apoptosis in cell lines with constitutive c-Met activity. These cellular responses to ARQ 197 were phenocopied by RNAi-mediated c-Met depletion and further demonstrated by the growth inhibition of human tumors following oral administration of ARQ 197 in multiple mouse xenograft efficacy studies. Cumulatively, these data suggest that ARQ 197, currently in phase II clinical trials, is a promising agent for targeting cancers in which c-Met-driven signaling is important for their survival and proliferation.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Neru Munshi", "Sébastien Jeay", "Youzhi Li", "Chang-Rung Chen", "Dennis S. France", "Mark A. Ashwell", "Jason E. Hill", "Magdi Moussa", "David Leggett", "Chiang J. Li"], "yil": 2010}
{"atif_sayisi": 1367, "atiflar": ["W1498131948", "W1545201063", "W1967821919", "W1971915141", "W1979993283", "W1982298394", "W1988908019", "W1992925554", "W1994807255", "W1998762942", "W1999319877", "W2011312875", "W2022914311", "W2028244585", "W2034152669", "W2035936653", "W2043620856", "W2047980471", "W2051788298", "W2052396334", "W2052750950", "W2053333277", "W2067381705", "W2070044720", "W2086262311", "W2089528428", "W2090895449", "W2096931514", "W2097981550", "W2104373322", "W2124690619", "W2127971542", "W2132755748", "W2135129680", "W2138778824", "W2144508375", "W2161576473", "W2186603104", "W2301131921", "W2318564252", "W2407748472", "W4290194648"], "baslik": "The specificities of protein kinase inhibitors: an update", "doi": "https://doi.org/10.1042/bj20021535", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Kinase", "DYRK1A", "Biochemistry", "Protein-Serine-Threonine Kinases", "Protein kinase A", "Cyclin-dependent kinase", "Biology", "Threonine"], "kimlik": "W2011588737", "ozet": "We have previously examined the specificities of 28 commercially available compounds, reported to be relatively selective inhibitors of particular serine/threonine-specific protein kinases [Davies, Reddy, Caivano and Cohen (2000) Biochem. J. 351, 95-105]. In the present study, we have extended this analysis to a further 14 compounds. Of these, indirubin-3'-monoxime, SP 600125, KT 5823 and ML-9 were found to inhibit a number of protein kinases and conclusions drawn from their use in cell-based assays are likely to be erroneous. Kenpaullone, Alsterpaullone, Purvalanol, Roscovitine, pyrazolopyrimidine 1 (PP1), PP2 and ML-7 were more specific, but still inhibited two or more protein kinases with similar potency. Our results suggest that the combined use of Roscovitine and Kenpaullone may be useful for identifying substrates and physiological roles of cyclin-dependent protein kinases, whereas the combined use of Kenpaullone and LiCl may be useful for identifying substrates and physiological roles of glycogen synthase kinase 3. The combined use of SU 6656 and either PP1 or PP2 may be useful for identifying substrates of Src family members. Epigallocatechin 3-gallate, one of the main polyphenolic constituents of tea, inhibited two of the 28 protein kinases in the panel, dual-specificity, tyrosine-phosphorylated and regulated kinase 1A (DYRK1A; IC(50)=0.33 microM) and p38-regulated/activated kinase (PRAK; IC(50)=1.0 microM).", "tam_metin_adresi": null, "yayinci": "Portland Press", "yazarlar": ["Jenny Bain", "Hilary McLauchlan", "Matthew Elliott", "Philip Cohen"], "yil": 2003}
{"atif_sayisi": 267, "atiflar": ["W111932728", "W120676909", "W198571108", "W1485850033", "W1490860457", "W1569865130", "W1581824937", "W1592467150", "W1701250584", "W1725436419", "W1752312133", "W1778117100", "W1839348318", "W1874305637", "W1995819749", "W2016086822", "W2031390067", "W2043869143", "W2058839845", "W2069637592", "W2073700431", "W2097384422", "W2099226150", "W2109960839", "W2132150864", "W2138172881", "W2138302361", "W2140927361", "W2144383844", "W2154027407", "W2167537652", "W2259515764", "W2314938037", "W3044574244"], "baslik": "The selective tyrosine kinase inhibitor STI571 inhibits small cell lung cancer growth.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Tyrosine kinase", "Platelet-derived growth factor receptor", "Stem cell factor", "Protein kinase B", "Biology", "Tyrosine-kinase inhibitor", "Autocrine signalling", "Receptor tyrosine kinase"], "kimlik": "W2151493026", "ozet": "At least 70% of small cell lung cancers express the Kit receptor tyrosine kinase and its ligand, stem cell factor (SCF). Numerous lines of evidence have demonstrated that this coexpression constitutes a functional autocrine loop, suggesting that inhibitors of Kit tyrosine kinase activity could have therapeutic efficacy in this disease. STI571, formerly known as CGP 57148B, is a p.o. bioavailable 2-phenylaminopyrimide derivative that was designed as an Abl tyrosine kinase inhibitor, but also has efficacy against the platelet-derived growth factor receptor and Kit in vitro. Pretreatment of the H526 small cell lung cancer (SCLC) cell line with STI571 inhibited SCF-mediated Kit activation with an IC50 of 0.1 microM as measured by inhibition of receptor tyrosine phosphorylation and 0.2 microM as measured by immune complex kinase assay. This paralleled the inhibition of SCF-mediated growth by STI571, which had an IC50 of approximately 0.3 microM. Growth inhibition in SCF-containing medium was accompanied by induction of apoptosis. STI571 efficiently blocked SCF-mediated activation of mitogen-activated protein kinase and Akt, but did not affect insulin-like growth factor-1 or serum-mediated mitogen-activated protein kinase or Akt activation. Growth of five of six SCLC cell lines in medium containing 10% FCS was inhibited by STI571 with an IC50 of approximately 5 microM. Growth inhibition in serum-containing medium appeared to be cytostatic in nature because no increase in apoptosis was observed. Despite this growth inhibition, STI571 failed to enhance the cytotoxicity of either carboplatinum or etoposide when coadministered. However, taken together with the minimal toxicity that this compound has shown in preclinical studies, these data suggest that STI571 could have a role in the treatment of SCLC, possibly to block or slow recurrence after chemotherapy-induced remissions.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Geoffrey W. Krystal", "Sittisak Honsawek", "Julie Litz", "Elisabeth Buchdunger"], "yil": 2000}
{"atif_sayisi": 240, "atiflar": ["W1964378600", "W1982848861", "W1985032297", "W1993133483", "W1993357468", "W2000840258", "W2001097406", "W2006632173", "W2011588737", "W2014582878", "W2017356685", "W2018431023", "W2021730076", "W2022232710", "W2023040612", "W2029867653", "W2030687437", "W2030971064", "W2035753075", "W2039559098", "W2042775591", "W2058848030", "W2059665597", "W2062482627", "W2067405360", "W2072961231", "W2078146328", "W2085336624", "W2086957099", "W2091236030", "W2098499111", "W2100772783", "W2103268811", "W2111115182", "W2113414630", "W2114869204", "W2117022661", "W2119177802", "W2119694628", "W2141955227", "W2155836103", "W2157531111", "W2163341755", "W2170883726", "W2171445884", "W2612812586", "W2949159129", "W4285719527"], "baslik": "Structurally Sophisticated Octahedral Metal Complexes as Highly Selective Protein Kinase Inhibitors", "doi": "https://doi.org/10.1021/ja1112996", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Chemistry", "Coordination sphere", "Octahedron", "Selectivity", "Metal", "Molecule", "Stereochemistry", "Small molecule"], "kimlik": "W1978031869", "ozet": "The generation of synthetic compounds with exclusive target specificity is an extraordinary challenge of molecular recognition and demands novel design strategies, in particular for large and homologous protein families such as protein kinases with more than 500 members. Simple organic molecules often do not reach the necessary sophistication to fulfill this task. Here, we present six carefully tailored, stable metal-containing compounds in which unique and defined molecular geometries with natural-product-like structural complexity are constructed around octahedral ruthenium(II) or iridium(III) metal centers. Each of the six reported metal compounds displays high selectivity for an individual protein kinase, namely GSK3α, PAK1, PIM1, DAPK1, MLCK, and FLT4. Although being conventional ATP-competitive inhibitors, the combination of the unusual globular shape and rigidity characteristics, of these compounds facilitates the design of highly selective protein kinase inhibitors. Unique structural features of the octahedral coordination geometry allow novel interactions with the glycine-rich loop, which contribute significantly to binding potencies and selectivities. The sensitive correlation between metal coordination sphere and inhibition properties suggests that in this design, the metal is located at a \"hot spot\" within the ATP binding pocket, not too close to the hinge region where globular space is unavailable, and at the same time not too far out toward the solvent where the octahedral coordination sphere would not have a significant impact on potency and selectivity. This study thus demonstrates that inert (stable) octahedral metal complexes are sophisticated structural scaffolds for the design of highly selective chemical probes.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Feng Li", "Yann Geisselbrecht", "S. Blanck", "Alexander Wilbuer", "G. Ekin Atilla‐Gokcumen", "P. Filippakopoulos", "Katja Kräling", "Mehmet Ali Çelik", "Klaus Harms", "Jasna Maksimoska", "Ronen Marmorstein", "Gernot Frenking"], "yil": 2011}
{"atif_sayisi": 234, "atiflar": ["W4770467", "W59441890", "W1597787921", "W1965244935", "W1965418020", "W1969253200", "W1974227996", "W1984135408", "W1989792368", "W1993268216", "W2000007398", "W2000797437", "W2002070939", "W2003305442", "W2010282977", "W2014728730", "W2020706943", "W2035427061", "W2037180336", "W2048443661", "W2057492153", "W2070124738", "W2073251400", "W2077298757", "W2090213540", "W2091090974", "W2092310248", "W2098703441", "W2107744694", "W2107771085", "W2109219483", "W2123988706", "W2131897774", "W2132314214", "W2138214694", "W2138742704", "W2142804141", "W2144949163", "W2145410423", "W2149194612", "W2153939421", "W2163003098", "W2166403487", "W2259108511", "W2321522617", "W2335586700", "W2402247680", "W4247298916"], "baslik": "Inhaled Rho Kinase Inhibitors Are Potent and Selective Vasodilators in Rat Pulmonary Hypertension", "doi": "https://doi.org/10.1164/rccm.200405-637oc", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Thoracic Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Thoracic Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Fasudil", "Medicine", "Pulmonary hypertension", "Hypoxic pulmonary vasoconstriction", "Vasodilation", "Rho kinase inhibitor", "Rho-associated protein kinase", "Nitric oxide"], "kimlik": "W2137508241", "ozet": "We have found in chronically hypoxic rats that acute intravenous administration of the Rho kinase inhibitor Y-27632 nearly normalizes the pulmonary hypertension (PH) but has no pulmonary vascular selectivity. In this study, we tested if oral or inhaled Y-27632 would be an effective and selective pulmonary vasodilator in hypoxic PH. Although acute oral Y-27632 caused a marked and sustained decrease in mean pulmonary arterial pressure (MPAP), it also decreased mean systemic arterial pressure (MSAP). In contrast, 5 minutes of inhaled Y-27632 decreased MPAP without reducing MSAP. The hypotensive effect of inhaled Y-27632 on hypoxic PH was greater than that of inhaled nitric oxide, and the effect lasted for at least 5 hours. Inhaled fasudil, another Rho kinase inhibitor, caused selective MPAP reductions in monocrotaline-induced PH and in spontaneous PH in fawn-hooded rats, as well as in chronically hypoxic rats. These results suggested that inhaled Y-27632 was more effective than inhaled nitric oxide as a selective pulmonary vasodilator in hypoxic PH, and that Rho kinase-mediated vasoconstriction was also involved in the other models of PH. Inhaled Rho kinase inhibitors might be useful for acute vasodilator testing in patients with PH, and future work should evaluate their efficacy in the long-term treatment of PH.", "tam_metin_adresi": null, "yayinci": "American Thoracic Society", "yazarlar": ["Tetsutaro Nagaoka", "Karen A. Fagan", "Sarah A. Gebb", "Kenneth G. Morris", "Tsutomu Suzuki", "Hiroaki Shimokawa", "Ivan F. McMurtry", "Masahiko Oka"], "yil": 2004}
{"doi": "https://doi.org/10.1038/nsmb.1818", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2111127068"}
{"doi": "https://doi.org/10.1038/40187", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W1597787921"}
{"atif_sayisi": 72, "atiflar": ["W229176803", "W1493414055", "W1598104848", "W1974790290", "W1990732986", "W1993487598", "W2000946764", "W2007245358", "W2015249545", "W2021218223", "W2045891127", "W2045956897", "W2050596106", "W2053806341", "W2064688277", "W2067133996", "W2076892293", "W2088451454", "W2090304113", "W2114278094", "W2131265653", "W2133614172", "W2137570167", "W2148371225", "W2341350186", "W2402295041", "W4301887097"], "baslik": "Prevention of Cardiac Allograft Arteriosclerosis by Protein Tyrosine Kinase Inhibitor Selective for Platelet-Derived Growth Factor Receptor", "doi": "https://doi.org/10.1161/01.cir.99.17.2295", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`Lippincott Williams & Wilkins`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "Lippincott Williams & Wilkins"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Medicine", "Platelet-derived growth factor", "Platelet-derived growth factor receptor", "Endocrinology", "Growth factor", "Tumor necrosis factor alpha", "Tyrosine kinase", "Internal medicine"], "kimlik": "W1969552991", "ozet": "BACKGROUND: Increased immunoreactivity of platelet-derived growth factor (PDGF)-AA, -Ralpha, and -Rbeta in intimal cells correlates with the development of cardiac allograft arteriosclerosis, a condition for which there is little or no current therapy. Therefore, we hypothesized that PDGF may have a rate-limiting role in the development of this disease. METHODS AND RESULTS: The hypothesis was tested in a rat model of heterotopic cardiac and aortic allografts using dark agouti (AG-B4, RT1(a)) donors and Wistar-Furth (AG-B2, RT1(u)) recipients. The recipients received CGP 53716, a selective PDGF-R protein tyrosine kinase inhibitor, 50 mg. kg-1. d-1, or vehicle for 60 days. Cardiac allograft recipients also received background cyclosporin A immunosuppression. Our results demonstrate that CGP 53716 significantly reduced the incidence and intensity of arteriosclerotic lesions in rat cardiac and aortic allograft recipients. When rat coronary smooth muscle cells were stimulated in vitro with PDGF-AA or -BB in the presence of interleukin-1beta or tumor necrosis factor-alpha, CGP 53716 significantly inhibited only AA-ligand-induced but not BB-ligand-induced replication. Concomitantly, in quantitative reverse transcriptase-polymerase chain reaction, interleukin-1beta or tumor necrosis factor-alpha stimulation specifically upregulated the expression of PDGF-Ralpha mRNA but not of other ligand or receptor genes in cultured smooth muscle cells. CONCLUSIONS: We conclude that a PDGF-AA/Ralpha-dependent cycle is induced in the generation of allograft arteriosclerosis that may be inhibited by blocking of signaling downstream of PDGF-R.", "tam_metin_adresi": null, "yayinci": "Lippincott Williams & Wilkins", "yazarlar": ["Roope Sihvola", "Petri Koskinen", "Marjukka Myllärniemi", "Michael Loubtchenkov", "P Häyry", "Elisabeth Buchdunger", "Karl Lemström"], "yil": 1999}
{"doi": "https://doi.org/10.1038/s41591-018-0007-9", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2801651204"}
{"atif_sayisi": 61, "atiflar": ["W305771979", "W1498142612", "W1590306163", "W1819068535", "W1831607674", "W1889134367", "W1922937805", "W1967411514", "W1971655733", "W1973454785", "W1976211465", "W2009667219", "W2010005988", "W2018074547", "W2018217843", "W2065710602", "W2069253625", "W2082910935", "W2085909636", "W2148824045", "W2216501506", "W2417181054", "W3106068331", "W6825536156"], "baslik": "Protein kinase inhibitors selectively block phorbol ester- or forskolin- induced changes in excitability of Aplysia neurons", "doi": "https://doi.org/10.1523/jneurosci.09-02-00473.1989", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Aplysia", "Forskolin", "Protein kinase C", "Phorbol ester", "Protein kinase A", "Chemistry", "Phorbol", "Cell biology"], "kimlik": "W1859823396", "ozet": "Exposure of the bag cell neurons of Aplysia to activators of protein kinase C, such as phorbol esters, enhances electrically evoked action potentials by increasing the voltage-dependent calcium current. We have hypothesized that this effect is mediated by the activation of protein kinase C (PKC). An important prediction of this hypothesis is that inhibitors of PKC should inhibit these phorbol ester-induced changes in bag cell neuronal excitability. We have now found that treatment of bag cell neurons with the protein kinase inhibitor 1-[5-isoquinolinesulfonyl]-2-methyl piperazine (H-7) inhibits the phorbol ester-induced enhancement of bag cell action potentials and prevents the enhancement of calcium current by phorbol esters. The height and width of electrically evoked action potentials in bag cell neurons can also be enhanced by cAMP analogs or agents that elevate cAMP. These agents do not influence the major voltage-dependent calcium current in the bag cell neurons but may act by modulating potassium currents and other voltage-dependent currents. We have found that microinjection of a protein inhibitor of cAMP-PK (PKA-I) into isolated bag cell neurons prevents and reverses the effect of the adenylate cyclase activator forskolin on action potentials of these cells. In contrast, H-7 does not inhibit the effects of forskolin on a variety of responses in these cells, including its effects on action potentials, granule movement, and 32P incorporation into phosphoproteins. This suggests that H-7 is selective for PKC relative to cAMP-PK in intact bag cell neurons.", "tam_metin_adresi": null, "yayinci": "Society for Neuroscience", "yazarlar": ["P. Jeffrey Conn", "J.A. Strong", "EM Azhderian", "Angus C. Nairn", "Paul Greengard", "LK Kaczmarek"], "yil": 1989}
{"atif_sayisi": 185, "atiflar": ["W29325754", "W68102770", "W1568505377", "W1971241026", "W2004037911", "W2009618725", "W2010992064", "W2014582878", "W2015390918", "W2016761176", "W2028428863", "W2035936653", "W2052750950", "W2060818930", "W2065289702", "W2078261279", "W2084882261", "W2103268811", "W2107614388", "W2116096636", "W2133289340", "W2135817940", "W2140472738", "W2157395284", "W2157761330", "W2161471780", "W2166318113", "W2167368929", "W2171258641", "W2171773992", "W2172057280", "W2319831517", "W2329125394", "W4247904703"], "baslik": "Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase", "doi": "https://doi.org/10.1158/1535-7163.mct-06-0397", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["PIM1", "Kinase", "Biology", "Biochemistry", "Enzyme inhibitor", "Chemistry", "Protein kinase A", "Serine"], "kimlik": "W2126595940", "ozet": "The pim-1 kinase is a true oncogene that has been implicated in the development of leukemias, lymphomas, and prostate cancer, and is the target of drug development programs. We have used experimental approaches to identify a selective, cell-permeable, small-molecule inhibitor of the pim-1 kinase to foster basic and translational studies of the enzyme. We used an ELISA-based kinase assay to screen a diversity library of potential kinase inhibitors. The flavonol quercetagetin (3,3',4',5,6,7-hydroxyflavone) was identified as a moderately potent, ATP-competitive inhibitor (IC(50), 0.34 micromol/L). Resolution of the crystal structure of PIM1 in complex with quercetagetin or two other flavonoids revealed a spectrum of binding poses and hydrogen-bonding patterns in spite of strong similarity of the ligands. Quercetagetin was a highly selective inhibitor of PIM1 compared with PIM2 and seven other serine-threonine kinases. Quercetagetin was able to inhibit PIM1 activity in intact RWPE2 prostate cancer cells in a dose-dependent manner (ED(50), 5.5 micromol/L). RWPE2 cells treated with quercetagetin showed pronounced growth inhibition at inhibitor concentrations that blocked PIM1 kinase activity. Furthermore, the ability of quercetagetin to inhibit the growth of other prostate epithelial cell lines varied in proportion to their levels of PIM1 protein. Quercetagetin can function as a moderately potent and selective, cell-permeable inhibitor of the pim-1 kinase, and may be useful for proof-of-concept studies to support the development of clinically useful PIM1 inhibitors.", "tam_metin_adresi": null, "yayinci": "American Association for Cancer Research", "yazarlar": ["Sheldon L. Holder", "Marina Zemskova", "Chao Zhang", "M. Tabrizizad", "Ryan Bremer", "Jonathan W. Neidigh", "Michael B. Lilly"], "yil": 2007}
{"doi": "https://doi.org/10.1016/0006-291x(91)92031-e", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W565127267"}
{"atif_sayisi": 1580, "atiflar": ["W1528279723", "W1530970237", "W1547974121", "W1550017207", "W1553713007", "W1568928604", "W1570470675", "W1571844404", "W1589866689", "W1594758412", "W1595133660", "W1650137855", "W1755902553", "W1964839077", "W1973454785", "W1980854090", "W1983985175", "W1993282564", "W1995499596", "W2007319015", "W2015648136", "W2020257412", "W2032017706", "W2035999317", "W2050338578", "W2050844193", "W2051531396", "W2055802474", "W2075473225", "W2088072731", "W2091673674", "W2096077209", "W2102153963", "W2117227310", "W2142339245", "W2156565205", "W2325489425", "W2345218661", "W2426793753", "W3127324270"], "baslik": "Selective inhibition of protein kinase C isozymes by the indolocarbazole Gö 6976", "doi": "https://doi.org/10.1016/s0021-9258(18)98335-3", "gerekce": "opt-out yayıncı `Elsevier BV` bu eseri kendi konumunda `cc-by` ile yayımlamış", "gerekce_kodu": "opt_out_ama_acik_lisans", "gerekce_param": {"lisans": "cc-by", "yayinci": "Elsevier BV"}, "izin": "TAM", "kavramlar": ["Isozyme", "Chemistry", "Biochemistry", "Molecular biology", "Genetics", "Enzyme", "Biology"], "kimlik": "W1641731911", "ozet": "Indolocarbazoles have been identified as novel inhibitors of protein kinase C (PKC), with Gö 6976 as one of its most potent and selective representatives. Recombinant PKC isozymes alpha, beta 1, delta, epsilon, and zeta were used in in vitro kinase assays to investigate Gö 6976 with respect to isozyme-specific PKC inhibition. Gö 6850, identical with GF 109203X, another PKC-specific kinase inhibitor, was included in this study as a reference compound. Nanomolar concentrations of the indolocarbazole Gö 6976 inhibited the Ca(2+)-dependent isozymes alpha and beta 1, whereas even micromolar concentration of Gö 6976 had no effect on the kinase activity of the Ca(2+)-independent PKC subtypes delta, epsilon, and zeta. In contrast, the bisindolymaleimide Gö 6850 inhibited all PKC isozymes, however, with a ranked order of potency (alpha > beta 1 > epsilon > delta > zeta). Kinetic analysis revealed that PKC inhibition by Gö 6976 was competitive with respect to ATP, non-competitive with respect to the protein substrate, and mixed type with respect to phosphatidylserine. Further experiments in the presence of different amounts of free Ca2+ indicated that interference with Ca2+ or its binding site is not responsible for the differential inhibition of PKC isozymes by Gö 6976.", "tam_metin_adresi": "https://doi.org/10.1016/s0021-9258(18)98335-3", "yayinci": "Elsevier BV", "yazarlar": ["Georg Martiny‐Baron", "Marcelo G. Kazanietz", "Harald Mischak", "Peter M. Blumberg", "Georg Kochs", "Hubert Hug", "Dieter Marmé", "Christoph Schächtele"], "yil": 1993}
{"atif_sayisi": 274, "atiflar": ["W1964203908", "W1964603185", "W1980577287", "W1982209220", "W1988026792", "W2050537958", "W2071156666", "W2106942695", "W2113929218", "W2128553601", "W2136284645", "W2140760855", "W2150703483", "W2156089500", "W2157153074", "W2179819010", "W3049347071", "W4253853981"], "baslik": "Discovery, Synthesis, and in Vivo Activity of a New Class of Pyrazoloquinazolines as Selective Inhibitors of Aurora B Kinase", "doi": "https://doi.org/10.1021/jm061335f", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Aurora B kinase", "In vivo", "Prodrug", "Chemistry", "Kinase", "Aurora inhibitor", "Aurora kinase", "Pharmacology"], "kimlik": "W2029335488", "ozet": "The Aurora kinases have been the subject of considerable interest as targets for the development of new anticancer agents. While evidence suggests inhibition of Aurora B kinase gives rise to the more pronounced antiproliferative phenotype, the most clinically advanced agents reported to date typically inhibit both Aurora A and B. We have discovered a series of pyrazoloquinazolines, some of which show greater than 1000-fold selectivity for Aurora B over Aurora A kinase activity, in recombinant enzyme assays. These compounds have been designed for parenteral administration and achieve high levels of solubility by virtue of their ability to be delivered as readily activated phosphate derivatives. The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous pharmacokinetic properties and safety pharmacology profiles. The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Andrew Mortlock", "Kevin M. Foote", "Nicola M. Heron", "Frédéric Jung", "Georges Pasquet", "Jean-Jacques M. Lohmann", "Nicolas Warin", "Fabrice Renaud", "Chris De Savi", "Nicola Roberts", "Trevor Johnson", "Cyril B. Dousson"], "yil": 2007}
{"atif_sayisi": 327, "atiflar": ["W23176963", "W145627486", "W1499176799", "W1523693806", "W1614056212", "W1898758687", "W1923816168", "W1964279184", "W1964881184", "W1972774425", "W1973837499", "W1981015006", "W1981817858", "W1987642183", "W1990450608", "W1992170852", "W1993835711", "W1996072280", "W1998836974", "W1999163644", "W2002228383", "W2007114641", "W2013131355", "W2015235010", "W2015705112", "W2015714994", "W2016441216", "W2017810288", "W2020094759", "W2021012077", "W2027731629", "W2029754521", "W2033999408", "W2043312574", "W2046584993", "W2053038488", "W2057370954", "W2059348339", "W2064746187", "W2067216245", "W2070732456", "W2082379606", "W2082416335", "W2082796078", "W2090256844", "W2092645471", "W2097645517", "W2099160414", "W2104540148", "W2105252089", "W2106687367", "W2111941456", "W2113892331", "W2120138780", "W2123023764", "W2126326200", "W2127311525", "W2128710251", "W2141300809", "W2142060283", "W2146157811", "W2148267502", "W2148861521", "W2153607816", "W2154836325", "W2154871907", "W2161281929", "W2162325356", "W2344829769", "W4238567307", "W4251893551", "W4252782193", "W4253103382", "W6600957040", "W6639624183", "W7075326444"], "baslik": "Characterization of VPS34-IN1, a selective inhibitor of Vps34, reveals that the phosphatidylinositol 3-phosphate-binding SGK3 protein kinase is a downstream target of class III phosphoinositide 3-kinase", "doi": "https://doi.org/10.1042/bj20140889", "gerekce": "açık lisans `cc-by` ticari TDM'e izin veriyor", "gerekce_kodu": "acik_lisans", "gerekce_param": {"lisans": "cc-by"}, "izin": "TAM", "kavramlar": ["Phosphatidylinositol", "Kinase", "Phosphoinositide 3-kinase", "Phosphorylation", "Endosome", "PI3K/AKT/mTOR pathway", "Cell biology", "Biochemistry"], "kimlik": "W2162889213", "ozet": "The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we describe a highly selective and potent inhibitor of Vps34, termed VPS34-IN1, that inhibits Vps34 with 25 nM IC50 in vitro, but does not significantly inhibit the activity of 340 protein kinases or 25 lipid kinases tested that include all isoforms of class I as well as class II PI3Ks. Administration of VPS34-IN1 to cells induces a rapid dose-dependent dispersal of a specific PtdIns(3)P-binding probe from endosome membranes, within 1 min, without affecting the ability of class I PI3K to regulate Akt. Moreover, we explored whether SGK3 (serum- and glucocorticoid-regulated kinase-3), the only protein kinase known to interact specifically with PtdIns(3)P via its N-terminal PX domain, might be controlled by Vps34. Mutations disrupting PtdIns(3)P binding ablated SGK3 kinase activity by suppressing phosphorylation of the T-loop [PDK1 (phosphoinositide-dependent kinase 1) site] and hydrophobic motif (mammalian target of rapamycin site) residues. VPS34-IN1 induced a rapid ~50-60% loss of SGK3 phosphorylation within 1 min. VPS34-IN1 did not inhibit activity of the SGK2 isoform that does not possess a PtdIns(3)P-binding PX domain. Furthermore, class I PI3K inhibitors (GDC-0941 and BKM120) that do not inhibit Vps34 suppressed SGK3 activity by ~40%. Combining VPS34-IN1 and GDC-0941 reduced SGK3 activity ~80-90%. These data suggest SGK3 phosphorylation and hence activity is controlled by two pools of PtdIns(3)P. The first is produced through phosphorylation of PtdIns by Vps34 at the endosome. The second is due to the conversion of class I PI3K product, PtdIns(3,4,5)P3 into PtdIns(3)P, via the sequential actions of the PtdIns 5-phosphatases [SHIP1/2 (Src homology 2-domain-containing inositol phosphatase 1/2)] and PtdIns 4-phosphatase [INPP4B (inositol polyphosphate 4-phosphatase type II)]. VPS34-IN1 will be a useful probe to delineate physiological roles of the Vps34. Monitoring SGK3 phosphorylation and activity could be employed as a biomarker of Vps34 activity, in an analogous manner by which Akt is used to probe cellular class I PI3K activity. Combining class I (GDC-0941) and class III (VPS34-IN1) PI3K inhibitors could be used as a strategy to better analyse the roles and regulation of the elusive class II PI3K.", "tam_metin_adresi": "https://portlandpress.com/biochemj/article-pdf/463/3/413/680497/bj4630413.pdf", "yayinci": "Portland Press", "yazarlar": ["Ružica Bago", "Nazma Malik", "Michael J. Munson", "Alan R. Prescott", "Paul Davies", "Eeva Sommer", "Natalia Shpiro", "Richard A. Ward", "Darren A.E. Cross", "Ian G. Ganley", "Dario R. Alessi"], "yil": 2014}
{"atif_sayisi": 624, "atiflar": ["W1546139069", "W1964050579", "W1976161806", "W2008312146", "W2041581075", "W2047887493", "W2048399342", "W2049885874", "W2053442171", "W2068055557", "W2079791855", "W2080100430", "W2089198803", "W2097731764", "W2098786698", "W2120736516", "W2125262828", "W2126530235", "W2128327076", "W2129181924", "W2137368432", "W2147646344", "W2152354289", "W2154372386", "W2163285372", "W2952742739", "W4242150291"], "baslik": "Discovery of 7-Methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1 H -indol-5-yl)-7 H -pyrrolo[2,3- d ]pyrimidin-4-amine (GSK2606414), a Potent and Selective First-in-Class Inhibitor of Protein Kinase R (PKR)-like Endoplasmic Reticulum Kinase (PERK)", "doi": "https://doi.org/10.1021/jm300713s", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Endoplasmic reticulum", "Chemistry", "Protein kinase R", "Trifluoromethyl", "Kinase", "Unfolded protein response", "Protein kinase A", "Apoptosis"], "kimlik": "W2161371655", "ozet": "Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small molecule inhibitors. Through screening and lead optimization using the human PERK crystal structure, we discovered compound 38 (GSK2606414), an orally available, potent, and selective PERK inhibitor. Compound 38 inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Jeffrey M. Axten", "Jesús R. Medina", "Yanhong Feng", "Arthur Y. L. Shu", "Stuart P. Romeril", "Seth W. Grant", "William Hoi Hong Li", "Dirk A. Heerding", "Elisabeth A. Minthorn", "Thomas Mencken", "Charity Atkins", "Qi Liu"], "yil": 2012}
{"doi": "https://doi.org/10.1016/j.bmcl.2003.10.062", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2178382797"}
{"doi": "https://doi.org/10.1016/0006-291x(90)91544-3", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2085547973"}
{"doi": "https://doi.org/10.1053/j.seminoncol.2011.01.016", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2078964293"}
{"doi": "https://doi.org/10.1038/nrd.2018.21", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2794211762"}
{"atif_sayisi": 500, "atiflar": [], "baslik": "Pharmacological profile of SB 203580, a selective inhibitor of cytokine suppressive binding protein/p38 kinase, in animal models of arthritis, bone resorption, endotoxin shock and immune function.", "doi": "https://doi.org/10.1016/s0022-3565(25)21307-6", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Society for Pharmacology and Experimental Therapeutics`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Society for Pharmacology and Experimental Therapeutics"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Cytokine", "Arthritis", "Pharmacology", "Medicine", "Bone resorption", "Immune system", "Tumor necrosis factor alpha", "In vivo"], "kimlik": "W1921708445", "ozet": null, "tam_metin_adresi": null, "yayinci": "American Society for Pharmacology and Experimental Therapeutics", "yazarlar": ["A M Badger", "Jeremy N. Bradbeer", "Bartholomew J. Votta", "J C Lee", "Jerry L. Adams", "Don E. Griswold"], "yil": 1996}
{"doi": "https://doi.org/10.1016/s0960-894x(01)00344-4", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2062366098"}
{"atif_sayisi": 750, "atiflar": ["W255996521", "W1486786974", "W1529396499", "W1580424021", "W1594020010", "W1797430954", "W1964503089", "W1972919751", "W1978686683", "W1983113139", "W2009555064", "W2020372547", "W2035008060", "W2052750950", "W2059411043", "W2070732456", "W2070841378", "W2079977894", "W2085483616", "W2087861588", "W2107614388", "W2109099165", "W2109467838", "W2115484306", "W2129172946", "W2159530979", "W2161810908", "W2164139183", "W2388163742", "W2415437540", "W4247904703", "W4253109001"], "baslik": "The Identification of 2-(1 H -Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2- d ]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer", "doi": "https://doi.org/10.1021/jm800295d", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Chemistry", "Phosphatidylinositol", "PI3K/AKT/mTOR pathway", "Pyrimidine", "Kinase", "Pharmacology", "Protein kinase B", "Stereochemistry"], "kimlik": "W2029754521", "ozet": "Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Adrian Folkes", "Khatereh Ahmadi", "W. Alderton", "Sonia Alix", "Stewart Baker", "Gary Box", "Irina Chuckowree", "Paul A. Clarke", "Paul Depledge", "Suzanne A. Eccles", "Lori S. Friedman", "Angela Hayes"], "yil": 2008}
{"doi": "https://doi.org/10.1016/j.bmcl.2005.09.072", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Elsevier BV` (P4310320990) `Elsevier BV` grubuna ait: TDM Click-through lisansı ticari TDM için ayrı izin şart koşuyor · 24,2M eser"}, "izin": "ENGELLI", "kimlik": "W2175513472"}
{"doi": "https://doi.org/10.1038/sj.cdd.4400436", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2067530043"}
{"atif_sayisi": 215, "atiflar": ["W277606711", "W1528483543", "W1537044333", "W1963723282", "W1966041739", "W1973466091", "W1983790923", "W1989013915", "W1993148712", "W1998791246", "W1999968212", "W2008517160", "W2014123957", "W2015518146", "W2016011980", "W2040475550", "W2047649751", "W2050041795", "W2051531396", "W2066468520", "W2067455153", "W2068229957", "W2079726617", "W2093369908", "W2093611899", "W2096023298", "W2097233276", "W2123269248", "W2129381779", "W2146672317", "W2152503709", "W2160842779", "W2951803487", "W4320065062", "W4327849160"], "baslik": "Discovery of a Potent and Selective Protein Kinase CK2 Inhibitor by High-Throughput Docking", "doi": "https://doi.org/10.1021/jm030827e", "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`American Chemical Society`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "American Chemical Society"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Docking (animal)", "Chemistry", "Virtual screening", "Homology modeling", "Drug discovery", "Enzyme inhibitor", "Computational biology", "Enzyme"], "kimlik": "W1973180272", "ozet": "To assess the potential of protein kinase CK2 as a target for developing new antitumor agents, we have undertaken a search for inhibitors of this enzyme. As part of this effort, we report here the discovery of the potent and selective CK2 inhibitor (5-oxo-5,6-dihydroindolo[1,2-a]quinazolin-7-yl)acetic acid. We identified this inhibitor of a novel structural type by high-throughput docking of our corporate compound collection in the ATP binding site of a homology model of human CK2, using an appropriate protocol. The synthesis of the inhibitor as well as that of related analogues whose CK2 inhibitory activities give support to the binding mode proposed by the docking program is described. The results obtained suggest that virtual screening of a 3D database by molecular docking is a useful approach for lead finding provided that adapted postdocking filtering and reranking procedures are applied to the primary hit list.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Eric Vangrevelinghe", "Kaspar Zimmermann", "Joseph Schoepfer", "Robert Ernst Portmann", "Doriano Fabbro", "Pascal Furet"], "yil": 2003}
{"atif_sayisi": 262, "atiflar": ["W1990472274", "W2012563646", "W2106494998", "W2106930740", "W2114852376", "W2124662474", "W2128542677", "W2154196978", "W2163188200", "W2166262263", "W2171003891"], "baslik": "Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors", "doi": "https://doi.org/10.1021/ml4000063", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Dabrafenib", "Melanoma", "Kinase", "In vivo", "Cancer research", "In vitro", "Mutant", "V600E"], "kimlik": "W2079104985", "ozet": "Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-Raf(V600E) mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GSK2118436, a selective inhibitor of Raf kinases with potent in vitro activity in oncogenic B-Raf-driven melanoma and colorectal carcinoma cells and robust in vivo antitumor and pharmacodynamic activity in mouse models of B-Raf(V600E) human melanoma. GSK2118436 was identified as a development candidate, and early clinical results have shown significant activity in patients with B-Raf mutant melanoma.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["Tara Rheault", "John Stellwagen", "George M. Adjabeng", "Keith R. Hornberger", "Kimberly G. Petrov", "Alex G. Waterson", "Scott H. Dickerson", "Robert A. Mook", "Sylvie Laquerre", "Alastair J. King", "Olivia W. Rossanese", "Marc R. Arnone"], "yil": 2013}
{"doi": "https://doi.org/10.1038/nchembio.83", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Nature Portfolio` (P4310319908) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W2158662692"}
{"atif_sayisi": 569, "atiflar": ["W1549650288", "W1605768520", "W1613040252", "W1909881335", "W1917630072", "W1939561089", "W1997785224", "W2002776738", "W2007317685", "W2007928608", "W2008313660", "W2011460845", "W2018877148", "W2024282024", "W2032674547", "W2036498316", "W2042923157", "W2049196962", "W2053002668", "W2056961869", "W2058792197", "W2061234826", "W2074356752", "W2103565638", "W2114464348", "W2118310862", "W2132633540", "W2156719646", "W2170418913", "W2173560213", "W2175994433", "W2313848691", "W2410073144", "W2766442484"], "baslik": "Discovery of JSI-124 (cucurbitacin I), a selective Janus kinase/signal transducer and activator of transcription 3 signaling pathway inhibitor with potent antitumor activity against human and murine cancer cells in mice.", "doi": null, "gerekce": "telifli görünüyor (lisans=`None`, yayıncı=`National Institutes of Health`) ve opt-out ilan edilmemiş — yalnız meta-veri", "gerekce_kodu": "telifli", "gerekce_param": {"kumeYasi": "", "lisans": "", "yayinci": "National Institutes of Health"}, "izin": "YALNIZ_METAVERI", "kavramlar": ["STAT3", "Janus kinase", "Cancer research", "STAT protein", "Proto-oncogene tyrosine-protein kinase Src", "Signal transduction", "Protein kinase B", "Biology"], "kimlik": "W1584223654", "ozet": "Constitutively activated, tyrosine-phosphorylated signal transducer and activator of transcription (STAT) 3 plays a pivotal role in human tumor malignancy. To discover disrupters of aberrant STAT3 signaling pathways as novel anticancer drugs, we developed a phosphotyrosine STAT3 cytoblot. Using this high throughput 96-well plate assay, we identified JSI-124 (cucurbitacin I) from the National Cancer Institute Diversity Set. JSI-124 suppressed the levels of phosphotyrosine STAT3 in v-Src-transformed NIH 3T3 cells and human cancer cells potently (IC(50) value of 500 nM in the human lung adenocarcinoma A549) and rapidly (complete inhibition within 1-2 h). The suppression of phosphotyrosine STAT3 levels resulted in the inhibition of STAT3 DNA binding and STAT3-mediated but not serum response element-mediated gene transcription. JSI-124 also decreased the levels of tyrosine-phosphorylated Janus kinase (JAK) but not those of Src. JSI-124 was highly selective for JAK/STAT3 and did not inhibit other oncogenic and tumor survival pathways such as those mediated by Akt, extracellular signal-regulated kinase 1/2, or c-Jun NH(2)-terminal kinase. Finally, JSI-124 (1 mg/kg/day) potently inhibited the growth in nude mice of A549 tumors, v-Src-transformed NIH 3T3 tumors, and the human breast carcinoma MDA-MB-468, all of which express high levels of constitutively activated STAT3, but it did not affect the growth of oncogenic Ras-transformed NIH 3T3 tumors that are STAT3 independent or of the human lung adenocarcinoma Calu-1, which has barely detectable levels of phosphotyrosine STAT3. JSI-124 also inhibited tumor growth and significantly increased survival of immunologically competent mice bearing murine melanoma with constitutively activated STAT3. These results give strong support for pharmacologically targeting the JAK/STAT3 signaling pathway for anticancer drug discovery.", "tam_metin_adresi": null, "yayinci": "National Institutes of Health", "yazarlar": ["Michelle A. Blaskovich", "Jiazhi Sun", "Alan Cantor", "James Turkson", "Richard Jove", "Saı̈d M. Sebti"], "yil": 2003}
{"atif_sayisi": 252, "atiflar": ["W265208425", "W1501954618", "W1583531858", "W1813485308", "W1971553338", "W1973195696", "W1982411778", "W1990651432", "W1997513635", "W2009289049", "W2016408686", "W2019216438", "W2023746688", "W2033867789", "W2034623756", "W2052690081", "W2052940891", "W2054526083", "W2062458432", "W2071549499", "W2078275018", "W2093522627", "W2103820395", "W2115629214", "W2131531959", "W2133192145", "W2145138842", "W2154066874", "W2157486761", "W2161482291", "W2163167085", "W2163431182", "W2163690533", "W2167854315", "W2169226551", "W2171771895", "W2171990314", "W2172609141", "W2207535250", "W2237058775", "W2250687747", "W2255241835", "W2316021978", "W2320793684", "W2323400728", "W2340488228", "W2405533405", "W2513274461", "W2518577288", "W2564350518", "W2571078282", "W2587684973", "W2594910449", "W2604620912", "W2611512307", "W2736041638", "W2886313452", "W4205407880", "W4253960665"], "baslik": "Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development", "doi": "https://doi.org/10.1021/acs.jmedchem.7b01712", "gerekce": "açık erişim işaretli ama lisans belirtilmemiş — erişilebilirlik, ticari kullanım izni değildir", "gerekce_kodu": "acik_erisim_lisanssiz", "gerekce_param": {}, "izin": "YALNIZ_METAVERI", "kavramlar": ["Bruton's tyrosine kinase", "Tyrosine kinase", "Chemistry", "Pharmacology", "Rheumatoid arthritis", "Tyrosine-kinase inhibitor", "Arthritis", "Cancer research"], "kimlik": "W2788356134", "ozet": "Bruton's tyrosine kinase (Btk) is a nonreceptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Preclinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and preclinical characterization of a potent, selective, and noncovalent Btk inhibitor currently in clinical development. GDC-0853 (29) suppresses B cell- and myeloid cell-mediated components of disease and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2 studies ongoing in patients with rheumatoid arthritis, lupus, and chronic spontaneous urticaria. On the basis of its potency, selectivity, long target residence time, and noncovalent mode of inhibition, 29 has the potential to be a best-in-class Btk inhibitor for a wide range of immunological indications.", "tam_metin_adresi": null, "yayinci": "American Chemical Society", "yazarlar": ["James J. Crawford", "Adam R. Johnson", "Dinah Misner", "Lisa D. Belmont", "Georgette M. Castanedo", "Regina Choy", "Melis Coraggio", "Liming Dong", "Charles Eigenbrot", "Rebecca J. Erickson", "Nico Ghilardi", "Jonathan Hau"], "yil": 2018}
{"doi": "https://doi.org/10.1038/sj.onc.1207810", "gerekce": "yayıncı TDM opt-out: yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser", "gerekce_kodu": "yayinci_opt_out", "gerekce_param": {"neden": "yayıncı kimliği `Springer Nature` (P4310319965) `Springer Nature` grubuna ait: TDM için ayrı lisans gerekiyor · 2,8M eser"}, "izin": "ENGELLI", "kimlik": "W1969482148"}