IC50: 9.8 nM (squalene epoxidase, in HepG2 cell homogenates)

Serum lipid levels in hamsters after daily administration of FR194738 and Pravastatin for 10 d are measured. FR194738 reduces the serum levels of total, non high density lipoprotein (HDL) and HDL cholesterol, and triglyceride. Treatment of hamsters with FR194738 increases HMG-CoA reductase activity by 1.3-fold at 32 mg/kg compared to the control group and does not significantly change that at 100 mg/kg.

In intact HepG2 cells, FR194738 concentration-dependently inhibits the incorporation of [ 14 C]acetate into free cholesterol and cholesteryl ester, with IC 50 s of 4.9 and 8.0 nM, respectively. FR194738 induces intracellular [ 14 C]squalene accumulation. FR194738 increases the incorporation of [ 14 C]acetate into squalene, an intermediate of cholesterol synthesis. FR194738 potently inhibits squalene epoxidase (SE) in HepG2 cell homogenate and liver microsomes in dogs and rats. The inhibitory effect of FR194738 in comparison to the HMG-CoA reductase inhibitors, Simvastatin, Fluvastatin and Pravastatin, on cholesterol biosynthesis in HepG2 cells is examined. Among these compounds, FR194738 is the most potent, with an IC 50 of 2.1 nM. The IC 50 s of Simvastatin, Fluvastatin and Pravastatin are 40, 28 and 5100 nM, respectively. FR194738 inhibits hamster liver microsomal squalene epoxidase activity in a concentration-dependent manner with an IC 50 of 14 nM.

FR194738 free base 是一种角鲨烯环氧化酶 (squalene epoxidase) 抑制剂。在 HepG2 细胞匀浆中, FR194738 抑制角鲨烯环氧酶活性，IC50 值为 9.8 nM。