Effects of F-1394, an Acyl-CoA:Cholesterol Acyltransferase (ACAT) Inhibitor, on ACAT Activity in HepG2 Cells and on Hepatic Secretion of Lipids in Triton WR-1339-Induced Hyperlipidemic Rats: Possible Role of Hepatic ACAT in Very Low Density Lipoprotein Secretion

The Japanese Journal of Pharmacology

Haruo Ohnishi¹  Jun Kusunoki¹  Tetsuya Kitamine¹  Katsumi Aragane¹  Tetsuaki Yamaura¹ 

[1] Pharmaceuticals Research Laboratories, Fujirebio, Inc.

关键词: Acyl-CoA:cholesterol acyltransferase;    F-1394;    Triton WR-1339;   

DOI  :  10.1254/jjp.76.309

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(15)Cited-By(3)We examined the inhibitory potency of F-1394 ((1S, 2S)-2-[3-(2, 2-dimethylpropyl)-3-nonylureido]cyclohexane-1-yl 3-[(4R)-N-(2, 2, 5, 5-tetramethyl-1, 3-dioxane-4-carbonyl)amino]propionate), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on ACAT activity and its hypolipidemic effect. F-1394 inhibited whole-cell ACAT activity in HepG2 cells with an IC50 value of 42 nM. The potency of F-1394 was greater than that of the five other ACAT inhibitors tested (YM-17E, CI-976, 57-118, CL-277, 082 and DL-melinamide). In rats made hyperlipidemic by Triton WR-1339, F-1394 caused a reduction in the hepatic secretion rate of cholesterol. These data suggest that inhibition of hepatic ACAT activity helps to reduce very low density lipoprotein secretion from the liver into the circulation.

【 授权许可】

Unknown