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.
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.
Azuma
Y
Y
Central Research Institute, Nissin Food Products Co., Ltd., Kusatsu, Shiga, Japan.
Seto
J
J
Ohno
K
K
Mikami
H
H
Yamada
T
T
Yamasaki
M
M
Chiba
M
M
Nobuhara
Y
Y
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D018938:Caco-2 Cells; D002784:Cholesterol / Q000378:metabolism*; D003510:Cyclohexanes / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004951:Esterification / Q000187:drug effects; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D050356:Lipid Metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000814:Aniline Compounds; D003510:Cyclohexanes; D004791:Enzyme Inhibitors; C111531:NTE 122; D002784:Cholesterol; D002785:Sterol O-Acyltransferase