Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT. AMG 706 potently inhibited VEGF-induced but not bFGF-induced proliferation of HUVECs with IC50 values of 10 nmol/L and >3,000 nmol/L, respectively. Similarly, AMG 706 potently inhibited both PDGFinduced proliferation and SCF-induced c-kit phosphorylation with IC50 values of 207 and 37 nmol/L, respectively. AMG 706 displayed no activity against unrelated kinases as evidenced by the lack of activity against EGF-induced EGFR phosphorylation in A431 cells (IC50, >25 Amol/L).

1. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Polverino, A., Coxon, A., et al. 2006 Cancer Research 66 (17), pp. 8715-8721 2. Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Cabebe, E., Wakelee, H. 2007 Current treatment options in oncology 8 (1), pp. 15-27