As a selective inhibitor, AMG-208 can potently inhibit c-Met with IC50 of 9.3 nM. In PC3 cells, AMG-208 also can induce inhibition to c-Met phosphorylation mediated by HGF with IC50 of 46 nM.
In vivo
AMG-208 exhibits favorable pharmacokinetics and displayed potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver PD model. Once-daily oral administration of 24 for 22days showed significant tumor growth inhibition in an NIH-3T3/TPR-Met xenograft mouse efficacy model.