Melinamide, an amide derivative of an unsaturated long-chain fatty acid, is an inhibitor of cholesterol absorption with an IC50 of 20.9 uM.
DL-Melinamide inhibits acyl CoA:cholesterol acyltransferase activity (ACAT) in the mucosal microsomes, with 50% inhibition occurring at approximately 0.5 uM. Kinetic studies indicate that DL-Melinamide is an uncompetitive inhibitor of acyl CoA:cholesterol acyltransferase. D-Melinamide is found to be a more effective inhibitor than L-Melinamide[2].
Melinamide is a new hypocholesterolaemic drug. Melinamide causes a substantial decrease of the enhanced intestinal ACAT activity in diabetic rats, but does not affect intestinal cholesterol esterase activity. Furthermore, marked improvement of hypercholesterolaemia in cholesterol-fed diabetic rats occurrs concomitantly with the drug treatment[3].
References:
[1]. Kusunoki J, et al. Effect of F-1394, a potent and selective inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), on esterification of cholesterol and basolateral secretion of cholesteryl ester in Caco-2 cells Nihon Yakurigaku Zasshi. 1997 Dec;110(6):357-65.
[2]. Natori K, et al. Mechanism of the inhibition of cholesterol absorption by DL-melinamide: inhibition of cholesterol esterification. Jpn J Pharmacol. 1986 Dec;42(4):517-23.
[3]. Matsubara K, et al. Cholesterol-lowering effect of N-(alpha-methylbenzyl)linoleamide (melinamide) in cholesterol-fed diabetic rats. Atherosclerosis. 1988 Aug;72(2-3):199-204.