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 significantly reduced following administration of RPR107393, demonstrating a potent cholesterol-lowering effect in rats. Specifically, a 92% reduction in cholesterol biosynthesis is observed with a dose of 5 mg/kg, peaking one hour post-administration (10 mg/kg p.o.). This effect decreases to 74% six hours post-administration at the same dosage, with the half-life for 50% inhibition being approximately 7 hours. A more pronounced effect is seen 10 hours after administering a larger dose (25 mg/kg p.o.), achieving an 82% inhibition rate; however, this effect dissipates at 21 hours. Additionally, both Zaragozic acid and RPR107393 lead to an accumulation of radiolabeled diacid products in the liver, indicating a mechanism associated with the inhibition of cholesterol biosynthesis. Remarkably, repeated doses of RPR107393 (30 mg/kg p.o. b.i.d.) result in a substantial decrease in serum cholesterol, lowering it by 35% after two days and nearly 50% after three days of treatment.