Research Area: Solid tumours,Liver cancer,Gastrointestinal cancer
Biological Activity:
BMS-582664, also named “brivanib alaninate”, is the alaninate salt of a VEGFR2 inhibitor BMS-540215. Brivanib is hydrolyzed to the active moiety BMS-540215 in vivo. BMS-540215 shows potent and selective inhibition of VEGFR and FGFR tyrosine kinases [1,2] . BMS-540215 is an ATP-competitive inhibitor of human VEGFR-2, with an IC50 of 25 nM and Ki of 26 nmol/L. In addition, it inhibits VEGFR-1 (IC50 =380nM) and VEGFR-3 (IC50 = 10 nM). BMS-540215 also showed good selectivity for FGFR-1 (IC50=148 nM), FGFR-2 (IC50 =125 nM), and FGFR-3 (IC50 = 68 nM). Furthermore,BMS-540215 has been shown to selectively inhibit the proliferation of endothelial cells stimulated by VEGF and FGF in vitro with IC50 values of 40 and 276 nM, respectively[3,4] .BMS-582664 was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound BMS-540215.References on Brivanib alaninate (BMS-582664)[1] Clin Cancer Res, 2008, 14:6146-6153[2] J. Med. Chem, 2008, 51:1976–1980[3] Cancer Res, 2007, 67:6899-6906[4] Journal of Medicinal Chemistry, April 6, 2006, 49:2143-2146 |