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.

1999-01-01·Japanese journal of pharmacology

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

Article

作者: Masahiro Yamasaki ; Toshihiro Yamada ; Jiro Seto ; Hiroshi Mikami ; Yukimasa Azuma ; Masaru Chiba ; Yoichi Nobuhara ; Katsutoshi Ohno

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.

1999-01-01·Japanese journal of pharmacology

Effects of NTE-122, a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor, on Cholesterol Esterification and Secretions of Apolipoprotein B-Containing Lipoprotein and Bile Acids in HepG2

Article

作者: Masahiro Yamasaki ; Jiro Seto ; Toshihiro Yamada ; Takashi Kawasaki ; Yoichi Nobuhara ; Yukimasa Azuma ; Katsutoshi Ohno

We studied the effect of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylamino phenyl) ureido]methyl]cyclohexane), a novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, on intracellular cholesterol esterification and the secretion of apolipoprotein B100 (apoB)-containing lipoprotein and bile acids in the human hepatoma cell line HepG2. NTE-122 markably inhibited [3H]oleate incorporation into cholesteryl esters in HepG2 cells incubated with 5 microg/ml 25-hydroxycholesterol as a stimulus for ACAT (IC50=6.0 nM). On the other hand, NTE-122 did not affect [3H]oleate incorporation into triglycerides and phospholipids and [14C]acetate incorporation into cholesterol. The stimulation of ACAT by 25-hydroxycholesterol caused significant increases in the secretion of radiolabeled cholesteryl esters, radiolabeled triglycerides and apoB mass. NTE-122 pronouncedly inhibited the secretion of radiolabeled cholesteryl esters in proportion to the inhibition of cellular cholesterol esterification, and it significantly reduced the secretion of radiolabeled triglycerides and apoB mass in HepG2 cells incubated with 25-hydroxycholesterol. Furthermore, NTE-122 increased the secretion of bile acids synthesized from [14C]-cholesterol. These results suggest that NTE-122 is capable of exhibiting anti-hyperlipidemic effects by reducing both the cholesterol content and the amount of secreted very low-density lipoprotein and enhancing the excretion of bile acid from the liver.

100 项与 NTE-122 相关的药物交易

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