RPR107393 free base

RPR107393 free base is an orally active potent selective squalene synthase (SQS) inhibitor. RPR107393 free base inhibits rat liver microsomal squalene synthase with an IC₅₀ value of 0.8 nM. RPR107393 free base reduces triglyceride biosynthesis by suppressing fatty acid biosynthesis via an increase in intracellular farnesol and its derivatives. RPR107393 free base reduces plasma cholesterol in rats and marmosets. RPR107393 free base 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 free base (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 free base (6 h) concentration-dependently inhibits cholesterol biosynthesis (IC₅₀ = 880 nM) and triglyceride biosynthesis (IC₅₀ = 410 nM) in rat hepatocytes^[2].
RPR107393 free base (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 free base (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 free base (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 free base (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 free base (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 free base (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].