AMG-458 (AMG458) is a potent, selective, orally bioavailable c-Met inhibitor with Ki of 1.2 nM (human c-Met).
AMG-458 also potently binds to mutant c-Met (H1094R), c-Met (V1092I) and c-Met (D1228H) with Ki values of 0.5-2.2 nM.
AMG-458 inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM, abrogates the constitutive phosphorylation of c-Met in H441 cells.
AMG-458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models.
