Katsumi Aragane, Jun Kusunoki, Tetsuya Kitamine, Tetsuaki Yamaura and
Haruo Ohnishi
Pharmaceutical Research Laboratories, Fujirebio, Inc., 51 Komiya-cho,
Hachioji, Tokyo 192, Japan
Abstract: 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.
Keywords: Acyl-CoA:cholesterol acyltransferase, F-1394, Triton WR-1339