AMG-337 is an orally bioavailable, potent and exquisitely selective inhibitor of wild-type and some mutant forms of c-Met. In competitive binding assays on 402 human kinases, enantiomerically (optically) pure AMG-337 hits c-Met only (with an IC50 < 5 nM). In a cell viability study, the only cell lines that responded to an AMG 337 were gastric cancer cells harboring c-Met gene amplification. None of the other cell lines were sensitive to the AMG-337 and none harbored c-Met gene amplification. It inhibited HGF-dependent c-Met phosphorylation with an IC50 of less than 10 nM in cellular assay. Orally administered AMG-337 in c-Met amplified gastric cancer xenograft models resulted in a robust dose-dependent anti-tumor efficacy.

KEYWORDS: AMG-337 | c-Met kinase inhibitor | AMG377 | AMG 377 | CT-AMG337 | CAS [1173699-31-4] | HGF | c-MET | Inhibitor | Receptors