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. Y15 is a selective FAK inhibitor[1]. Treatment with Y15 caused decrease of p-FAK-Y397 in TT thyroid cancer cells at concentration of 1μM and 3μM, as well as decrease of both p-FAK-Y397 and FAK expression in TPC1, K1 and BCPAP thyroid cancer cells dose-dependently at concentration ranging 5-50μM. The cell viability showed that Y15 was much potent than Defactinib on growth inhibition of the four thyroid cancer cell lines, with IC50 values of 2.05μM, 5.74μM, 9.99μM and 17.54μM for TT, TPC1, BCPAP and K1 cells. The function of Y15 on this four cells through inhibition of FAK may due to increased detachment and necrosis, as well as decreased clonogenicity. Meanwhile, the distinct gene changes induced by Y15 from Defactinib may partially contribute to its synergism with Defactinib in medullary thyroid TT cells[2].
作用机制
Y15 can be docked into the structural pocket of FAK containing Y397 site.[1]
搜索
