AMG-208

AMG 208 is a small molecule inhibitor of c-Met, which inhibits both ligand-dependent and ligand-independent c-Met activation, IC50 = 9.3 nM. The c-MET pathway is dysregulated in most human malignancies, and regulates tumor formation, progression and dissemination, and numerous c-MET pathway inhibitors are currently being evaluated in the clinic. AMG-208 shows the inhibition of HGF-mediated c-Met phosphorylation in PC3 cells with IC50 of 46 nM. Pre-incubation of AMG-208 with human liver microsomes for 30 minutes shows a potent time-dependent inhibition for CYP3A4 metabolic activity with IC50 of 4.1 μM, which is an eightfold decrease relative to the IC50 (32 μM) without preincubation.