Brivanib

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).¹ 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.²

WARNING This product is not for human or veterinary use.

1. Bhide, R.S., Cai, Z.W., Zhang, Y.Z., et al. Discovery and preclinical studies of (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5- methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan- 2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J. Med. Chem. 49(7), 2143-2146 (2006).

2. Nakamura, I., Zakharia, K., Banini, B.A., et al. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling. PLoS One 9(4), e92273 (2014).