AMG-337

AMG-337 is a potent and selective inhibitor of MET with biochemical IC50 of 1 nM; inhibits of HGF-mediated MET phosphorylation in PC3 cells; shows desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model.Gastric Cancer Phase 2 Clinical (In Vitro) :AMG 337 (0-3 μM; 72 h) inhibits proliferation in MET-dependent cancer cell lines.AMG 337 (0-300 nM; 0-24 h; MKN-45, SNU-620, and SNU-5 cells) inhibits signaling through the PI3K and MAPK pathways in MET-amplified gastric cancer cell lines, resulting in an inhibition of MET-dependent cell proliferation and induction of apoptosis. (In Vivo) :AMG 337 (0-30 mg/kg; p.o.; daily, for 28 d) inhibits MET signaling in tumor xenografts and inhibits tumor growth in MET-dependent tumor xenograft models.AMG 337 (0-3 mg/kg; p.o.; once, for 3 or 24 h) is associated with increased necrosis in the MET-dependent SNU-620 tumor xenograft model.