RPR107393 free base is a selective inhibitor of squalene synthase(rat liver microsomal squalene synthase, with an IC50 of 0.8 nM).

Squalene synthase (rat liver microsomal):0.8±0.2 nM

RPR107393 is a selective inhibitor of squalene synthase with subnanomolar potency. Rat liver microsomal squalene synthase inhibited by RPR107393 (IC50 value of 0.8±0.2 nM (n=4))[1]. Cells are treated with ER-27856 (1 μM), RPR-107393 (10 μM), Atorvastatin (1 μM), or NB-598 (1 μM) for 2-24 h, and lipid biosynthesis during the last 2 h of the incubation is determined. RPR-107393 (10 μM) inhibits Cholesterol biosynthesis and reduces triglyceride biosynthesis. Similarly, 1 μM RPR-107393 inhibits Cholesterol and triglyceride biosynthesis by 82.4% and 70.0%, respectively[2].

Cholesterol biosynthesis is reduced by 92% (ED50 : 5 mg/kg),when one hour after RPR107393 (10 mg/kg p.o.). Six hours after RPR107393 (10 mg/kg p.o.) administration, Cholesterol biosynthesis is reduced by 74% (the time for 50% inhibition is ~7 hr). An 82% inhibition of hepatic Cholesterol biosynthesis is observed 10 hr after RPR107393 (25 mg/kg p.o.), but the effect is no longer apparent at 21 hr. Inhibition of Cholesterol biosynthesis by Zaragozic acid or RPR107393 is associated with an accumulation of radiolabeled diacid products in the liver. RPR107393 is a agent of potent Cholesterol-lowering in rats. RPR107393 (30 mg/kg p.o. b.i.d.) lowers serum Cholesterol by 35% after 2 days and by nearly 50% after 3 days of treatment[1].