FAK (Focal adhesion kinase), a non-receptor tyrosine kinase, can regulate the cytoskeleton and act as a scaffolding and signaling protein for other adhesion molecules. The expression of FAK and its phosphorylation status show a strong correlation with the invasive phenotype of aggressive human tumors. PF-562271 Besylate is the besylate form of PF-562271. PF-562271 is a potent and selective inhibitor for FAK and Pyk2 with IC50 values of 1.5nM and 14nM (measured by recombinant kinase assay), respectively, displaying over 100-fold selectivity against the other kinases tested[1]. PF-562271 showed robust inhibition on p-FAK with IC50 of 5nM in an inducible cell-based assay. Oral administration of PF-562271 can inhibit p-FAK in a dose-dependent fashion with calculated EC50 of 93ng/ml in the tumor-bearing mice, which suggesting the pharmacodynamics of this compound. In vitro study showed that PF-562271 had antitumor efficacy or caused tumor regression in multiple human s.c. xenograft models, including BxPC3, LoVo, U87MG, H125, PC3M and BT474, with dose ranging in 25-100mg/kg according to different models[1].
作用机制
PF-562271 can bind in the ATP-binding cleft of FAK and form two of the three H-bonds between PF-562271 and main-chain atoms in the kinase hinge region.[1]
PF-562271 besylate 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
ALL-PO cell
Growth inhibition assay
Inhibition of human ALL-PO cell growth in a cell viability assay, IC50=1.01584 μM
SANGER
human 8305C cell
Growth inhibition assay
Inhibition of human 8305C cell growth in a cell viability assay, IC50=1.09904 μM
SANGER
human AGS cell
Growth inhibition assay
Inhibition of human AGS cell growth in a cell viability assay, IC50=1.52124 μM
SANGER
human AN3-CA cell
Growth inhibition assay
Inhibition of human AN3-CA cell growth in a cell viability assay, IC50=1.21867 μM
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