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Ro 48-8071 is an inhibitor of OSC(Oxidosqualene cyclase; IC50=6.5 nM) that has low-density lipoprotein (LDL) cholesterol lowering activity. Ro 48-8071 blocked human liver OSC and cholesterol synthesis in HepG2 cells in the nanomolar range. In cells it triggered the production of monooxidosqualene, dioxidosqualene, and epoxycholesterol. It was safe in hamsters, squirrel monkeys and Göttingen minipigs at pharmacologically active doses, lowering LDL approximately 60% in hamsters, and at least 30% in the two other species, being at least as efficacious as safe doses of simvastatin. Ro 48-8071 did not reduce coenzyme Q10 levels in liver and heart of hamsters, and importantly did not trigger an overexpression of hepatic HMG-CoA reductase, squalene synthase, and OSC itself. Ro 48-8071 dose-dependently inhibited 17β-estradiol (E2)-induced ERα responsive luciferase activity (IC50 value, ~10 µM), under conditions that were non-toxic to the cells. Ro 48-8071 was less effective against ERβ-induced luciferase activity. Androgen receptor (AR) mediated transcriptional activity was also reduced by Ro 48-8071.
| Molecular Weight | 448.37 |
| Formula | C23H27BrFNO2 |
| CAS Number | 161582-11-2 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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