1.TMP-153, a novel ACAT inhibitor, inhibits cholesterol absorption and lowers plasma cholesterol in rats and hamsters.
Sugiyama Y1, Ishikawa E, Odaka H, Miki N, Tawada H, Ikeda H. Atherosclerosis. 1995 Feb;113(1):71-8.
Effects of TMP-153, N-[4-(2-chlorophenyl)-6,7-dimethyl-3-quinolyl]-N'-(2,4-difluorophe nyl)urea, on intestinal and hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activities, cholesterol absorption and plasma cholesterol level in rats and hamsters were studied. TMP-153 has IC50 values of around 5-10 nM for the hepatic and intestinal ACAT from various animals. The most potent inhibition was observed in the intestinal ACAT from Golden hamsters (IC50 = 2.3 nM). The inhibition mode of TMP-153 was non-competitive for rat intestinal ACAT. TMP-153 inhibited cholesterol esterification both in human colonic adenocarcinoma cells, LS180, and in human hepatoma cells, HepG2 (IC50 = 150 nM and 330 nM, respectively). [14C]cholesterol and cold cholesterol absorption from the small intestine was markedly inhibited by oral administration of TMP-153 (1 mg/kg) without affecting lymph flow and triglyceride absorption. When the compound was given as a dietary admixture, plasma cholesterol was reduced in rats fed a cholesterol diet (ED50 = 0.
