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• W2275892313 abstract "The novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor CP-113,818 has been characterized in vitro against ACAT isolated from liver and intestine from a variety of species including human subjects, and in vivo in cholesterol-fed rats, hamsters, rabbits, and two species of nonhuman primates. CP-113,818 is a potent and specific inhibitor of liver and intestinal ACAT with IC50s ranging from 17 to 75 nM. This ACAT inhibitor also prevented the absorption of exogenous radiolabeled cholesterol in hamsters (ED50 = 6 micrograms/kg), rabbits (ED50 1/2 10 micrograms/kg), and cynomolgus and African green monkeys (40 and 26% inhibition at 10 mg/kg, respectively). CP-113,818 effectively prevented the increase in liver cholesterol levels in cholesterol-fed rats, hamsters, and rabbits. In lipoprotein characterization studies in rabbits, CP-113,818 selectively decreased apoB-containing lipoproteins (beta-VLDL, IDL, and LDL) and shifted the distribution of cholesterol from beta-VLDL, IDL, and LDL (96% before treatment to 81% after treatment) to HDL (4% before treatment to 19% after treatment). Finally, in monkeys, CP-113,818 significantly decreased LDL cholesterol by approximately 30% while either increasing HDL cholesterol (cynomolgus monkeys) or not affecting HDL cholesterol (African green monkeys), thereby improving the total plasma cholesterol/HDL ratios. In summary, CP-113,818 significantly inhibited cholesterol absorption, prevented the increase in liver cholesterol, and improved the lipoprotein profiles by selectively decreasing the cholesterol concentrations of the atherogenic lipoproteins (VLDL, IDL, and LDL) in a variety of cholesterol-fed animals. These data suggest that ACAT inhibition may be a useful therapeutic approach for lowering LDL cholesterol and thereby reducing the risk of developing coronary heart disease." @default.
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• W2275892313 date "1994-10-01" @default.
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• W2275892313 title "Pharmacological properties of a novel ACAT inhibitor (CP-113,818) in cholesterol-fed rats, hamsters, rabbits, and monkeys" @default.
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• W2275892313 doi "https://doi.org/10.1016/s0022-2275(20)39778-9" @default.
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