Vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR and FLK1) is a receptor tyrosine kinase that regulates angiogenesis, vascular development, and embryonic hematopoiesis in response to VEGF isoforms A, C, and D. Ki8751 is a potent, orally available inhibitor of the kinase activity of VEGFR2 (IC50 = 0.9 nM). It less potently inhibits c-Kit, PDGRFα, and FGFR2 (IC50s = 40-170 nM) and has no significant effect against several other receptor tyrosine kinases. Ki8751 suppresses the growth of VEGF-stimulated human umbilical vein endothelial cells at nanomolar concentrations. It shows significant anti-tumor activity against assorted human tumor xenografts in nude mice. Ki8751 also induces cellular senescence in colorectal cancer cells.
