1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECerivastatinCat. No.: HY-129458CAS No.: 145599-86-6分式: CHFNO分量: 459.55作靶點(diǎn): HMG-CoA Reductase (HMGCR); Ferroptosis作通路: Metabolic Enzyme/Protease; Apoptosis儲存式: Please store the product under the recommended conditions inthe COA.B

2、IOLOGICAL ACTIVITY物活性 Cerivastatin種合成的降脂劑，種效，耐受性好，服活性的 HMG-CoA 還原酶抑制劑，Ki 為 1.3nM/L。Cerivastatin 可降低低密度脂蛋膽醇平。Cerivastatin 還主通過 RhoA 抑制作來抑制 MDA-MB-231 細(xì)胞的增殖和侵襲，具有抗癌作。IC50 & Target Ki: 1.3 nM/L (HMG-CoA reductase) 1 2 3體外研究Cerivastatin (5-50 ng/mL; 3 days; MDA-MB-231 cells) treatment induces a dose-dep

3、endent decrease in cellproliferation of MDA-MB-231 cells (up to 40% inhibition at 25 ng/mL) 1.Cerivastatin (25 ng/mL; 18-36 hours; MDA-MB-231 cells) treatment induces an arrest of the cell cycle in G1/S phase after 36 h treatment. This arrest is not observed for a shorter incubation time (18 h) 1.Ce

4、rivastatin (25 ng/mL; 18 hours; MDA-MB-231 cells) treatment induces a marked increase in the level ofp21Waf1/Cip1 1.Cerivastatin (25 ng/mL; 12 hours; MDA-MB-231 cells) treatment increases the p21 transcript in MDA-MB-231cells 1.Cerivastatin (10-25 ng/mL; 18 hours) inhibits invasion of MDA-MB-231 cel

5、ls through Matrigel 1.Cerivastatin (25 ng/mL; 18-36 hours) delocalizes RhoA and Ras from the membrane to the cytosol andinduces morphological changes 1.Cerivastatin (25 ng/mL; 4-36 hours) induces inactivation of NFB, in a RhoA inhibition-dependent manner,resulting in a decrease in urokinase and meta

6、lloproteinase-9 expression, and concomitantly increases IB1.Cell Proliferation Assay 11/3 Master of Small Molecules 您邊的抑制劑師www.MedChemECell Line: MDA-MB-231 cellsConcentration: 5 ng/mL, 10 ng/mL, 25 ng/mL, 50 ng/mLIncubation Time: 3 daysResult: Induced a dose-dependent decrease in cell proliferation

7、 of MDA-MB-231 cells.Cell Cycle Analysis 1Cell Line: MDA-MB-231 cellsConcentration: 25 ng/mLIncubation Time: 18 hours, 36 hoursResult: Induced a cell cycle block in G 1/S phase.Western Blot Analysis 1Cell Line: MDA-MB-231 cellsConcentration: 25 ng/mLIncubation Time: 18 hoursResult: Induced a marked

8、increase in the level of p21Waf1/Cip1.RT-PCR 1Cell Line: MDA-MB-231 cellsConcentration: 25 ng/mLIncubation Time: 12 hoursResult: Increased p21Waf1/Cip1 mRNA levels.體內(nèi)研究 Cerivastatin is well absorbed, reaching maximal plasma levels in 1-3 hours following oral dosing. In thecirculation, Cerivastatin i

9、s highly bound to plasma proteins (99.5%), with an elimination half-life of 2-4 hours.Cerivastatin is metabolized predominantly in the liver to three polar metabolites. Two of these metabolites areactive, but to a lesser extent compared to parent drug, and the third metabolite is inactive. Plasmacon

10、centrations of all metabolites are substantially lower than those of the parent drug. Elimination ofmetabolites is via the urine (20-25%) and feces (66-73%), while essentially no parent compound is excreted2.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Denoyelle C, et al. Cerivastat

11、in, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness andmetastatic properties of highly invasive breast cancer cell lines: an in vitro study. Carcinogenesis. 2001 Aug;22(8):1139-48.2. Stein E, et al. Cerivastatin, a New Potent Synthetic HMG Co-A Reductase Inhibitor: Effect of 0.2 mg Daily in Subjects With PrimaryHypercholesterolemia. J Cardiovasc Pharmacol Ther. 1997 Jan;2(1):7-16.3. Furberg CD, et al. Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2(5):205-207.McePdfHeightCaution: Pro