AMG-706 (Motesanib) is an orally-available, nicotinamide-based, ATP-competitive inhibitor of the VEGFR family of kinases, KIT, and PDGFR with IC50s of 2, 3, and 6 nM, 8 nM, and 84 nM (for VEGFR1, VEGFR2, and VEGFR3), respectively. Besides Ret activity (IC50 = 59 nM), AMG-706 is highly selective against other unrelated kinases, including Src and EGFR. [1] AMG-706 potently inhibits VEGF-induced proliferation of HUVECs with IC50 values of 10 nM. PDGF-induced proliferation and SCF-induced c-Kit phosphorylation was also inhibited at IC50 values of 207 and 37 nM, respectively.

AMG-706 was shown to increase tumor response to radiation in UM-SCC1 and SCC-1483 xenografts of head and neck squamous cell carcinomas. [2]