In vitro study | PF-04217903 is more selective than Staurosporine or PF-02341066, PF-04217903 acts on c-Met more than 1000 times more selective than the other group of 208 kinases, and is more sensitive to c-Met oncogenic mutations. In addition to acting on WT c-Met,PF-04217903 also effectively inhibits c-Met-H1094R, c-Met-R988C, and c-Met-T1010I activities, with IC50 of 3.1 nM, 6.4 nM, and 6.7 nM, respectively, but has little inhibitory effect on c-Met-Y1230C, IC50 >10 μm. The combination of PF-04217903 and Sunitinib significantly inhibited endothelial cell proliferation, but not tumor cells B16F1, Tib6, EL4, and LLC. PF-04217903 significantly inhibited the growth of LXFA 526L and LXFA 1647L clones with IC50 of 16 nM and 13 nM, respectively, and the effect was enhanced when combined with Cetuximab. PF-04217903 effectively inhibits c-Met-driven biological processes such as growth, motility, invasion and morphological changes of a variety of tumor cells. 2 μm PF-04217903 treatment of GTL-16 cells, promoting cell death, involving down-regulation of phosphorylated 4E-BP1, ERK/MAPK-related proteins, and the PI3K/AKT pathway. |