Chemical Name : Cediranib (AZD2171)/Recentin
CAS : 288383-20-0
Solubility:Soluble in DMSO
Storage:-20C 2 years
A series of amino acid ester prodrugs of the dual VEGFR-2/FGFR-1 kinase inhibitor 1 (BMS-540215) was prepared in an effort to improve the aqueous solubility and oral bioavailability of the parent compound.The L-alanine prodrug 8 (also known as brivanib alaninate/BMS-582664��an orally available) was selected as a development candidate and is presently in phase II clinical trials.The potency of BMS-540215on the VEGFR-2 and FGFR-1 kinases revealed IC50 values of 25 nM and 148 nM, respectively. BMS-540215 inhibits both VEGF- and basic fibroblast growth factor�Cstimulated human umbilical vascular endothelial cell growth in vitro but does not inhibit tumor cell growth in vitro. In multiple preclinical models of human tumor xenografts, both BMS-582664 and BMS-540215 have shown potent antitumor activity when dosed orally on a once-a-day schedule with complete induction of tumor stasis.
1. Cai ZW, Zhang Y, Borzilleri RM, Qian L, Barbosa S, Wei D, Zheng X, Wu L, Fan J, Shi Z, Wautlet BS, Mortillo S, Jeyaseelan R Sr, Kukral DW, Kamath A, Marathe P, D'Arienzo C, Derbin G, Barrish JC, Robl JA, Hunt JT, Lombardo LJ, Fargnoli J, Bhide RS. Discovery of brivanib alaninate ((S)-((R)-1-(4-(4-fluoro-2-methyl-1H- indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate), a novel prodrug of dual vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1 kinase inhibitor (BMS-540215). J Med Chem. 2008 Mar 27;51(6):1976-80. Epub 2008 Feb 21. 2. Huynh H, Ngo VC, Fargnoli J, Ayers M, Soo KC, Koong HN, Thng CH, Ong HS, Chung A, Chow P, Pollock P, Byron S, Tran E. Brivanib alaninate, a dual inhibitor of vascular endothelial growth factor receptor and fibroblast growth factor receptor tyrosine kinases, induces growth inhibition in mouse models of human hepatocellular carcinoma. Clin Cancer Res. 2008 Oct 1;14(19):6146-53. 3. Ayers M, Fargnoli J, Lewin A, Wu Q, Platero JS. Discovery and validation of biomarkers that respond to treatment with brivanib alaninate, a small-molecule VEGFR-2/FGFR-1 antagonist. Cancer Res. 2007 Jul 15;67(14):6899-906.