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Acyl-CoA:cholesterol acyltransferase (ACAT) catalyses the esterification of excess cellular cholesterol with fatty acids and is important for intestinal cholesterol absorption, hepatic lipoprotein secretion, and cholesterol accumulation in vascular tissues. ACAT inhibitors improve plasma lipid profile and ameliorate proteinuria in nephrotic animals. TMP-153 is a quinolyl derivative that inhibits ACAT with IC50 values of 5-10 nM in various animals. At 0.5-1.5 mg/kg, TMP-153 dose-dependently reduces plasma total- and low density lipoprotein cholesterol without affecting high density lipoprotein cholesterol in hamsters. It inhibits cholesterol esterification both in human colonic adenocarcinoma L S180 cells and in human hepatoma HepG2 cells (IC50s = 150 and 330 nM, respectively). When fed as a dietary supplement (ED50 = 0.81 mg/kg/day), TMP-153 reduces hepatic cholesterogenesis in hamsters fed a stock diet.

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