Sunitinib malate

Sunitinib malate is a potent ATP-competitive and cell permeable multi-targeted receptor tyrosine kinase (RTK) inhibitor targeting VEGFR, PDGFR-beta and c-Kit (Ki = 2-17nM). It inhibits FLK1 (Ki=9nM), PDGFRbeta (Ki=8nM) and FLT3. It is at least 10-fold selective for FLK1 and PDGFRbeta over a variety of tyrosine kinases in a panel, including EGFR, Cdk2, Met, IGFR-1, Abl and Src. Sunitinib malate inhibits the cellular receptor phosphorylation of FLT3, RET and CSF-1R. Sunitinib malate exhibits potent antiangiogenic and antitumor activity in multiple xenograft models. It decreases VEGF- and FGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) and reduces tumor growth in a variety of mouse xenograft models when administered at doses ranging from 20 to 80 mg/kg per day.