YM-53601 free base

YM-53601 is a squalene synthase inhibitor (IC₅₀s = 79 and 90 nM in HepG2 cells and rat liver microsomes, respectively).¹ It inhibits cholesterol biosynthesis in rats (ED₅₀ = 32 mg/kg).¹ YM-53601 dose-dependently reduces plasma triglyceride and non-HDL cholesterol levels in hamsters fed both normal and high-fat diets. It also reduces viral RNA, core and NS3 protein production, and secreted viral particles in Huh7.5.1-8 cells infected with the hepatitis C virus (HCV) strain JFH-1 without affecting cell viability at concentrations ranging from 0.5 to 1.5 μM.² YM-53601 (1-10 μM) confers protection against cytotoxicity induced by the bacterial pore-forming toxin pneumolysin in HBE1 and normal human bronchial epithelial (NHBE) cells.³

1.Ugawa, T., Kakuta, H., Moritani, H., et al.YM-53601, a novel squalene synthase inhibitor, reduces plasma cholesterol and triglyceride levels in several animal speciesBr. J. Pharmacol.13163-70(2000) 2.Saito, K., Shirasago, Y., Suzuki, T., et al.Targeting cellular squalene synthase, an enzyme essential for cholesterol biosynthesis, is a potential antiviral strategy against hepatitis C virusJ. Virol.89(4)2220-2232(2015) 3.Statt, S., Ruan, J.W., Hung, L.Y., et al.Statin-conferred enhanced cellular resistance against bacterial pore-forming toxins in airway epithelial cellsAm. J. Respir. Cell Mol. Biol.53(5)689-702(2015)