BIBB 515

BIBB 515 is a potent, selective and orally active 2,3-oxidosqualene cyclase (OSC) inhibitor with ED₅₀ values of 0.2-0.5 mg/kg and 0.36-33.3 mg/kg in rats and mice (1-5 hours), respectively. BIBB 515 exerts lipid-lowering effect mainly by inhibiting the production of low-density lipoprotein (LDL)^[1]. IC50 & Target: 2,3-oxidosqualene cyclase (OSC)^[1] In Vitro: Sterol synthesis, 2,3-oxidosqualene cyclase activity, HMGCoA reductase activity, and the specificity of BIBB 51 5 versus 2,3-oxidosqualene cyclase are measured in intact HepG2 cells or cell homogenates.Concentration-dependent inhibition of cholesterol biosynthesis by BIBB 515 as monitored by [¹⁴C]-acetate incorporation into digitonin precipitable sterols could be demonstrated in HepG2 cells (ED₅₀ = 4.11 nM). A similar inhibition of OSC activity (ED₅₀= 8.69 nM) is seen in HepC2 cell homogenates. No inhibition of HMGCoA reductasc could be measured in HepG2 cell homogenates at concentrations of BIBB 515 up to 1 and 10 μM^[1]. In Vivo: BIBB 515 (16.0-148.2 mg/ kg; oral administration; daily; for 40 days; male golden Syrian hyperlipemic hamsters) treatment shows dose-dependent lipid-lowering activity in normolipemic hamsters (-19% for total cholesterol and -32% for VLDL + LDL cholesterol) and in hyperlipemic hamsters (-25% for total cholesterol and -59% for LDL-cholesterol)^[1].