Jpn. J. Pharmacol. 80 (1), 81-84 (1999)

Effects of NTE-122, an Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Cholesterol Esterification and Lipid Secretion From CaCo-2 Cells, and Cholesterol Absorption in Rats

Yukimasa Azuma, Jiro Seto, Katsutoshi Ohno, Hiroshi Mikami, Toshihiro Yamada, Masahiro Yamasaki, Masaru Chiba and Yoichi Nobuhara

Central Research Institute, Nissin Food Products Co., Ltd., 2247, Noji, Kusatsu, Shiga 525-0055, Japan

Abstract: The effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on cholesterol absorption was investigated. NTE-122 inhibited whole-cell ACAT activity in CaCo-2 cells, a human intestinal cell line, with an IC50 value of 4.7 nM. In CaCo-2 cells cultured on a membrane filter, NTE-122 pronouncedly inhibited the basolateral secretion of newly synthesized cholesteryl esters, and significantly reduced the basolateral secretion of newly synthesized triglycerides without influencing the cellular triglyceride synthesis. Furthermore, NTE-122 (1 mg/kg, p.o.) inhibited [14C]cholesterol absorption in rats. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing the absorption of dietary cholesterol.

Keywords: NTE-122, Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, Cholesterol absorption

Copyrightę The Japanese Pharmacological Society 1999

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