Effects of NTE-122, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Cholesterol Esterification and High-Density LipoproteinInduced Cholesterol Efflux in Macrophages

The Japanese Journal of Pharmacology

Kiyohito Ikemoto¹  Masahiro Yamasaki¹  Yukimasa Azuma¹  Takashi Kawasaki¹  Katsutoshi Ohno¹  Toshihiro Yamada¹  Yoichi Nobuhara¹ 

[1]Central Research Institute, Nissin Food Products Co., Ltd.

关键词: NTE-122;    Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor;    Macrophage;    Cholesterol accumulation;    Cholesterol efflux;   

DOI  :  10.1254/jjp.79.159

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(7)We investigated the effects of a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, NTE-122 (trans-1, 4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl)ureido]methyl]cyclohexane), on ACAT activities in macrophages originating from several species and high-density lipoprotein (HDL)-induced cholesterol efflux in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 cells. NTE-122 inhibited cell-free ACAT activities in human PMA-treated THP-1 cells and mouse J774.1 cells with IC50 values of 0.88 and 360 nM, respectively. NTE-122 competively inhibited the ACAT activity in PMA-treated THP-1 cells. NTE-122 also inhibited cellular ACAT activities in PMA-treated THP-1 cells, rat peritoneal macrophages and J774.1 cells with IC50 values of 3.5, 84 and 6800 nM, respectively. Furthermore, NTE-122 prevented cholesterol accumulation in PMA-treated THP-1 cells incubated with acetylated low density lipoprotein, simultaneously with HDL, while it caused accumulation of a significant amount of free cholesterol in the absence and even in the presence of HDL. NTE-122 also enhanced HDL-induced cholesterol efflux from established foam cells converted from PMA-treated THP-1 cells. These results suggest that NTE-122, capable of inhibiting macrophage ACAT activity in humans more strongly than those in the other species, exhibits anti-atherogenic effects by preventing the foam cell formation and enhancing the foam cell regression in humans.

【 授权许可】

Unknown