RPR107393

RPR107393 is an orally active potent selective squalene synthase (SQS) inhibitor. RPR107393 inhibits rat liver microsomal squalene synthase with an IC₅₀ value of 0.8 nM. RPR107393 reduces triglyceride biosynthesis by suppressing fatty acid biosynthesis via an increase in intracellular farnesol and its derivatives. RPR107393 reduces plasma cholesterol in rats and marmosets. RPR107393 can be used for metabolic disease research, such as hypercholesterolemia, hypertriglyceridemia and atherosclerosis^[1][2]. IC50 & Target:IC50: 0.8±0.2 nM (rat liver microsomal squalene synthase)^[1] In Vitro:RPR107393 (10 min) is a potent inhibitor of rat liver microsomal squalene synthase, with IC₅₀ values of 0.6 to 0.9 nM, and is inactive (3% inhibition at 1 mM) against HMG-CoA reductase from rat liver microsomes^[1].
RPR107393 (6 h) concentration-dependently inhibits cholesterol biosynthesis (IC₅₀ = 880 nM) and triglyceride biosynthesis (IC₅₀ = 410 nM) in rat hepatocytes^[2].
RPR107393 (10 μM, 2-24 h) decreases the incorporation of [1-¹⁴C]acetic acid into lipids in rat hepatocytes in a time-dependent manner, with maximal inhibition of cholesterol and triglyceride biosynthesis occurring at 2 h and 24 h, respectively^[2].
RPR107393 (1 μM, 4 h) inhibits cholesterol and triglyceride biosynthesis by 82.4% and 70.0% in rat hepatocytes, respectively, with the latter effect potentiated by MVL supplementation, suggesting a mechanism involving increased FPP derivatives^[2].
RPR107393 (1-10 μM, 4 h) increases carnitine-dependent mitochondrial β-oxidation (by 26.5% at 1 μM and 39.5% at 10 μM), it reduces overall triglyceride biosynthesis through a β-oxidation-independent pathway^[2].
RPR107393 (10 μM, 4 h) suppresses triglyceride biosynthesis in rat hepatocytes, reducing fatty acid and triglyceride synthesis by 67.7% and 68.5%, respectively, through inhibiting fatty acid synthesis rather than later metabolic stages^[2]. In Vivo:RPR107393 (10, 25 and 30 mg/kg, p.o., sigle dose, b.i.d. for 2-4 days, or q.d. for 7 days) exerts potent hypolipidemic effects after oral administration in rats^[1].
RPR107393 (20 mg/kg, p.o., b.i.d. or q.d. for 7 days) selectively lowers LDL cholesterol while maintaining a favorable HDL profile in marmosets^[1].