BMS-795311 是一种有效的，具有口服活性的胆固醇酯转移蛋白 CETP 抑制剂， IC50 值分别为 4 nM (SPA) 和 0.22 μM (hWPA)。
BMS-795311 (1-3 mg/kg; oral administration) inhibits plasma CE transfer activity in human CETP (hCETP)/apoB-100 dual transgenic (Tg) mice.
BMS-795311 (3-10 mg/kg; p.o. for 3 days) increases high density lipoprotein-cholesterol (HDL-C) content.
BMS-795311 (8 mg/kg, i.v.) has no effect on mean, systolic, or diastolic blood pressure, heart rate, or locomotor activity in rat telemetry studies.
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).
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).
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Animal Model:
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hCETP/apoB-100 dual Tg mice
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Dosage:
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1, 3 mg/kg
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Administration:
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Oral administration
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Result:
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Inhibited CETP activity at a dose of 1 mg/kg at the 8 h time point.
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Animal Model:
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Moderately fat-fed hamsters
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Dosage:
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3, 10 mg/kg
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Administration:
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Oral administration for 3 days
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Result:
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Increased plasma high density lipoprotein-cholesterol (HDL-C) content by 45% when dosed at 10 mg/kg.
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