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Ro 48-8071 fumarate

MCE China：Ro 48-8071 fumarate

Brand：MedChemExpress (MCE)

Cat. No.HY-18630A

CAS：189197-69-1

Purity：99.42%

Storage：4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Ro 48-8071 fumarate is an inhibitor of OSC (Oxidosqualene cyclase) with IC50 of appr 6.5 nM.

In Vitro：In HepG2 cells, Ro 48-8071 reduces cholesterol synthesis dose dependently with an IC50 value of appr 1.5 nM[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].

In Vivo：Ro 48-8071 lowers LDL-C maximally appr 60% at 150 μmol/kg per day, with no further reduction up to 300 μmol/kg per day, leaving HDL-C unchanged at all doses in hamsters. Ro 48-8071 (≥00 μmol/kg per day) increases the amount of MOS in liver of hamsters. Ro 48-8071 (300 μmol/kg per day) remarkedly and significantly reduces VLDL secretion of hamsters[1]. Ro 48-8071 (5 or 20 mg/kg) significantly reduces in vivo tumor growth in mice, without weight loss of the mice. Furthermore, Ro 48-8071 at a concentration of 20 mg/kg, completely eradicates two of the 12 tumors being monitored in the mice in the timeframe tested[2]. Ro 48-8071 (20 mg/day/kg body weight) leads to a rapid and sustained inhibition (>50%) of cholesterol synthesis in the whole small intestine of BALB/c mice. Sterol synthesis is also reduced in the large intestine and stomach[4].

Animal Administration：Six-week-old male athymic nude mice (nu/nu) weighing 20-22 g are used in the assay. Castration-resistant PC-3 cells (5×106 in 0.15 mL solution) are mixed with matrigel and RPMI-1640 medium (1/1, v/v) and injected subcutaneously into both flanks of each mouse (n=6 animals/group) and tumors allowed to develop. The tumors are measured twice per week with a digital caliper. Tumor volumes are calculated by the formula (L × W × H) × π/6. Drug treatment is started when tumor volumes reach appr 100 mm3. Mice are given daily tail vein injections of 0.1 mL solution of either 5 or 20 mg/kg Ro 48-8071 for 5 days. This is followed by an injection every other day for six additional treatments and then a final injection 2 hours prior to sacrifice. Control mice receive the same volume of phosphate-buffered saline on the same schedule. The animals are weighed and tumor volumes are measured twice weekly throughout the drug treatment period.

IC50 & Target：IC50: appr 6.5 nM (Oxidosqualene cyclase)[1] Cellular Effect Cell Line Type Value Description References

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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.  [Content Brief]

[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  [Content Brief]

[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.  [Content Brief]

[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.  [Content Brief]