BMS-795311

BMS-795311 is a potent and orally bioavailable inhibitor of cholesteryl ester transfer protein (CETP), with IC₅₀s of 4 nM in an enzyme-based scintillation proximity assay (SPA) and 0.22 μM in a human whole plasma assay (hWPA), respectively^[1]. IC50 & Target: IC50: 4 nM (CETP)^[1] In Vitro: BMS-795311 (10 μM; 24 hours) does not increase aldosterone synthase (CYP11B2) mRNA at 10 μM in H295R cells^[1]. In Vivo: BMS-795311 (1-3 mg/kg; oral administration) inhibits plasma CE transfer activity in human CETP (hCETP)/apoB-100 dual transgenic (Tg) mice^[1].
BMS-795311 (3-10 mg/kg; p.o. for 3 days) increases high density lipoprotein-cholesterol (HDL-C) content^[1].
BMS-795311 (8 mg/kg, i.v.) has no e?ect on mean, systolic, or diastolic blood pressure, heart rate, or locomotor activity in rat telemetry studies^[1].
BMS-795311 exhibits reasonable oral bioavailability (mice 37%, rats 37%, monkeys 20%, dogs 5%) and C_max (mice 5.3, rats 17, monkeys 1.7, dogs 0.43 ng/mL) following oral administration (mice 10, rats 10, monkeys 5, dogs 5 mg/kg)^[1].
BMS-795311 exhibits terminal elimination half-lives (mice 6, rats 7, monkeys >18, dogs 10 h) due to low plasma clearance (2.0, 0.9, 0.9, and 1.4 mL/min/kg respectively) combined with little volumes of distribution (0.8, 0.4, 0.9, and 0.6 L/kg respectively) following intravenous administration (mice 5, rats 1, monkeys 4, dogs 1 mg/kg)^[1].