Ro 48-8071

Oxidosqualene cyclase (OSC) is a microsomal enzyme that catalyzes the cyclization of monooxidosqualene to lanosterol in the cholesterol synthetic pathway.{8343,12383} Ro 48-8071 is an inhibitor of oxidosqualene cyclase (OSC) that has low-density lipoprotein (LDL) cholesterol lowering activity similar to the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor simvastatin.{13141} It inhibits OSC from human liver microsomes and HepG2 cells with IC50 values of approximately 6.5 nM and 1.5 nM, respectively.{13141} Ro 48-8071 lowered LDL cholesterol ~40% in hamsters at a dose of 150 µg/kg without affecting high-density lipoprotein levels and with no sign of liver toxicity.{13141} Ro 48-8071 increases cytochrome P3A mRNA and protein levels in primary rat and murine hepatocyte cultures with a maximal effect at 30 µM.{13142}