Open AccessNTE-122, an Acyl-CoA:Cholesterol Acyltransferase Inhibitor, Prevents the Progression of Atherogenesis in Cholesterol-Fed Rabbits
Author(s) -
Yukimasa Azuma,
Katsuhiro Date,
Katsutoshi Ohno,
Shoichiro Matsushiro,
Yoichi Nobuhara,
Toshihiro Yamada
Publication year - 2001
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.86.120
Subject(s) - sterol o acyltransferase , cholesterol , aorta , endocrinology , medicine , thoracic aorta , chemistry , aortic arch , lesion , cyclohexane , acyl coa , biochemistry , enzyme , pathology , lipoprotein , organic chemistry
The cholesterol-lowering and anti-atherosclerotic effects of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylaminophenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, were evaluated in 1% cholesterol diet-fed rabbits. NTE-122 (1, 3 and 10 mg/kg per day) lowered the total cholesterol levels in both plasma and liver dose-dependently (by 99% and 94% at 10 mg/kg per day, respectively). In the aortic wall of the rabbits given NTE-122, the atherosclerotic lesion area in both aortic arch and thoracic aorta were dose-dependently reduced (by 100% at 10 mg/kg per day), and the total cholesterol content in aortic arch was also lowered significantly at more than 3 mg/kg per day. These results suggest that NTE-122 is capable of exhibiting anti-atherosclerotic effects.