Ro 48-8071

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的 2,3-氧化角鲨烯环化酶 (OSC) 抑制剂，IC50 为 6.5 nM。

A potent 2,3-oxidosqualene cyclase (OSC) inhibitor with IC50 of 6.5 nM; 6 times less potent against hamster and Gottingen minipig liver OSC, and 10-times more potent against squirrel monkey liver OSC; blocks human liver OSC and cholesterol synthesis in HepG2 cells in the nanomolar range; triggers the production of monooxidosqualene, dioxidosqualene, and epoxycholesterol.Dyslipidemia Preclinical.

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

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. 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. 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.

Ro-488071

Others

Other Targets

Other Targets

Cardiovascular Disease

Dyslipidemia

161582-11-2

448.3684

C23H27BrFNO2

>98% (HPLC)

10 mM in DMSO

CN(CCCCCCOC1=CC(=C(C=C1)C(=O)C2=CC=C(C=C2)Br)F)CC=C

Methanone, (4-bromophenyl)[2-fluoro-4-[[6-(methyl-2-propen-1-ylamino)hexyl]oxy]phenyl]-

(-20℃)

With Ice Pack

≥ 2 years