产品描述:
Brivanib is an ATP-competitive inhibitor of human vascular endothelial growth factor receptors (VEGFRs) 1 and 2 and fibroblast growth factor receptor 1 (FGFR1; IC50s = 380, 25, and 148 nM, respectively, for the human recombinant proteins).{36328} It is selective for VEGFR1 and 2 and FGFR1 over PDGFRβ, EGFR, LCK, PKCα, and JAK3 (IC50s = >1,900 nM), however, it also inhibits recombinant mouse Flk1 with an IC50 value of 89 nM. In vitro, brivanib inhibits VEGF- and FGF-stimulated proliferation of human umbilical vein endothelial cells (HUVECs) with IC50 values of 40 and 276 nM, respectively. In vivo, brivanib inhibits tumor growth by 85% and 97% when administered at 60 and 90 mg/kg p.o., respectively, for 10 days in an H3396 breast cancer mouse xenograft model. Brivanib (25 mg/kg per day for 7 days, p.o.) inhibits bile duct ligation-induced liver fibrosis in mice and increases expression of PDGFβ, PDGFRβ, TGF-β1, TGF-β R2, FGF2, FGFR2, and VEGFR2 mRNAs.{36329}