Therapeutics: Cholesteryl ester transfer protein (CETP)
In vitro and rodent studies identified a triphenylethanamine-based inhibitor of CETP that could help treat atherosclerosis. Chemical synthesis and in vitro testing of triphenylethanamine analogs identified a lead compound (BMS-795311) that inhibited CETP with an IC50 of 3.8 nM. In transgenic mice expressing human CETP and in hamsters, the compound decreased CETP activity in plasma with comparable potency to the CETP inhibitor torcetrapib. In rats, BMS-795311 did not increase blood pressure - a known side effect of torcetrapib - compared with vehicle. Next steps could include testing BMS-795311 in animal models of atherosclerosis.
Bristol-Myers Squibb Co. and Simcere Pharmaceutical Group have BMS-795311 in preclinical testing for cardiovascular indications...