| Description | Ro 48-8071 fumarate is an inhibitor of OSC(Oxidosqualene cyclase; IC50=6.5 nM) that has low-density lipoprotein (LDL) cholesterol lowering activity. |
| In vitro | Ro 48-8071 在HepG2细胞中以剂量依赖的方式降低胆固醇合成，其IC50值约为1.5 nM[1]。Ro 48-8071 (10 μM) 显著降低了PC-3前列腺癌细胞的活性，但对正常前列腺细胞无显著影响。Ro 48-8071 (10-30 μM) 以剂量依赖的方式诱导LNCaP和C4-2细胞系的凋亡。24小时内使用Ro 48-8071治疗的去势抵抗型PC-3和DU145细胞也表现出显著的凋亡水平。Ro 48-8071 (10-25 μM) 以剂量依赖的方式减少AR蛋白表达。Ro 48-8071 (0.1-1 μM) 在依赖激素的LNCaP细胞和去势抵抗型PC-3细胞中以剂量依赖的方式增加ERβ蛋白表达[2]。使用被工程化的哺乳动物细胞表达人类ERα或ERβ蛋白，结合ER反应性的荧光素酶启动子，Ro 48-8071 以剂量依赖的方式抑制17β-雌二醇(E2)诱导的ERα反应性荧光素酶活性(IC50约为10 μM)，且这些条件对细胞无毒性[3]。 |
| In vivo | Ro 48-8071在每天150μmol/kg剂量下，可最大限度降低LDL-C约60%，增加至300μmol/kg每天剂量时，其降低效果不再提升，同时在所有剂量下对HDL-C无影响。Ro 48-8071在每天≥00μmol/kg剂量下，能显著增加仓鼠肝脏中MOS的含量。Ro 48-8071在每天300μmol/kg剂量下，显著且显着降低了仓鼠的VLDL分泌[1]。Ro 48-8071在5或20mg/kg剂量下，明显抑制了小鼠体内肿瘤生长，且不引起小鼠体重下降。而且，20mg/kg浓度的Ro 48-8071完全消除了在测试时间范围内监测的12个肿瘤中的两个[2]。Ro 48-8071以20mg/天/kg体重剂量，导致BALB/c小鼠全小肠胆固醇合成迅速且持久地抑制（>50%）。大肠和胃的固醇合成也有所降低[4]。 |
| Target activity | OSC:6.5 nM |
| molecular weight | 564.44 |
| Molecular formula | C27H31BrFNO6 |
| CAS | 189197-69-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 22.5 mg/mL (39.86 mM) |
| References | 1. Morand OH, et al. Ro 48-8.071, a new 2,3-oxidosqualene:lanosterol cyclase inhibitor lowering plasma cholesterol in hamsters, squirrel monkeys, and minipigs: comparison to simvastatin. J Lipid Res. 1997 Feb;38(2):373-90. 2. Liang Y, et al. Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells. Onco Targets Ther. 2016 May 30;9:3223-32. 3. Liang Y, et al. Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat. 2014 Jul;146(1):51-62. 4. Chuang JC, et al. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse. Biochem Pharmacol. 2014 Apr 1;88(3):351-63. |
| Citations | 1. Zhang L, Yi Y, Wang T, et al.25-Hydroxycholesterol inhibits classical swine fever virus entry into porcine alveolar macrophages by depleting plasma membrane cholesterol.Veterinary Microbiology.2023: 109668. 2. Liu Y, Wang Z, Jin H, et al.Squalene-epoxidase-catalyzed 24 (S), 25-epoxycholesterol synthesis promotes trained-immunity-mediated antitumor activity.Cell Reports.2024, 43(4). |