KRN-633

KRN-633 is a potent VEGFR inhibitor with IC₅₀s of 170, 160 and 125 nM for VEGFR1, VEGFR2 and VEGFR3, respectively. IC50 & Target: IC50: 170 nM (VEGFR1), 160 nM (VEGFR2), 125 nM (VEGFR3)^[1] In Vitro: KRN-633 inhibits tyrosine phosphorylation of VEGFR-1, VEGFR2, c-Kit, and PDGFR-β (IC₅₀=11.7, 1.16, 8.01, 130 nM) in human umbilical vein endothelial cells. KRN-633 also inhibits the VEGF-driven proliferation of HUVECs (IC₅₀=14.9 nM). KRN-633 suppresses capillary tube formation of endothelial cells^[1]. In Vivo: KRN-633 inhibits tumor growth in several tumor xenograft models with diverse tissue origins, including lung, colon, and prostate, in athymic mice and rats. KRN-633 also causes the regression of some well-established tumors and those that have regrown after the cessation of treatment. KRN-633 is well tolerated and has no significant effects on body weight or the general health of the animals. Histologic analysis of tumor xenografts treated with KRN-633 reveals a reduction in the number of endothelial cells in non-necrotic areas and a decrease in vascular permeability^[1].