Ro 48-8071 fumarate, an inhibitor of OSC (Oxidosqualene cyclase; IC50=6.5 nM), exhibits LDL (low-density lipoprotein) cholesterol-lowering activity.

OSC:6.5 nM

Ro 48-8071 reduces cholesterol synthesis dose-dependently with an IC50 value of appr 1.5 nM in HepG2 cells[1]. Ro 48-8071 (10 μM) significantly reduces the viability of PC-3 prostate cancer cells, but not normal prostate cells. Ro 48-8071 (10-30 μM) induces apoptosis of both LNCaP and C4-2 cell lines in a dose-dependent manner. And castration-resistant PC-3 and DU145 cells also demonstrate significant levels of apoptosis following 24-hour treatment with Ro 48-8071. Ro 48-8071 (10-25 μM) reduces AR protein expression in a dose-dependent manner. Ro 48-8071 (0.1-1 μM) increases ERβ protein expression dose-dependently in both hormone-dependent LNCaP and castration-resistant PC-3 cells[2]. Using mammalian cells engineered to express human ERα or ERβ protein, together with an ER-responsive luciferase promoter, Ro 48-8071 dose-dependently inhibits 17β-estradiol (E2)-induced ERα responsive luciferase activity (IC50, appr 10 μM), under conditions that are non-toxic to the cells[3].

Ro 48-8071 effectively reduces LDL-C by approximately 60% at a dose of 150 μmol/kg per day without further decrease at up to 300 μmol/kg per day, while not affecting HDL-C levels at any dose in hamsters. At doses of 300 μmol/kg per day or higher, it significantly elevates MOS levels in the liver and markedly diminishes VLDL secretion in hamsters. Additionally, Ro 48-8071, at 5 or 20 mg/kg, substantially curtails in vivo tumor growth in mice and completely eliminates two out of 12 monitored tumors at 20 mg/kg, without causing weight loss in the mice. Furthermore, at 20 mg/kg/day, it achieves a rapid and enduring suppression of more than 50% in cholesterol synthesis in the entire small intestine of BALB/c mice, along with reductions in sterol synthesis in the large intestine and stomach.