Cerivastatin (sodium salt)
(Synonyms: 西立伐他汀钠) 目录号 : GC43231An inhibitor of HMG-CoA reductase
Cas No.:143201-11-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cerivastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (Ki = 1.3 nM). It inhibits cholesterol synthesis in and growth of human arterial myocytes (IC50s = 0.4 and 4.6 nM, respectively). Cerivastatin inhibits proliferation of rat aorta smooth muscle cells and reduces fibrogen-induced migration of rat aortic myocytes in a concentration-dependent manner. In vivo, cerivastatin inhibits cholesterol biosynthesis in rats and dogs (ED50 = 0.002 mg/kg for both). It reduces serum levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) in dogs in a dose-dependent manner. Cerivastatin (0.1 mg/kg) decreases cholesterol ester accumulation in arterial tissue of rabbits fed a 0.2% cholesterol diet. It also stabilizes plaques and delays progression into atherosclerotic disease in LDL-receptor deficient rabbits with hypercholesterolemia.
| Cas No. | 143201-11-0 | SDF | |
| 别名 | 西立伐他汀钠 | ||
| Canonical SMILES | FC1=CC=C(C2=C(COC)C(C(C)C)=NC(C(C)C)=C2/C=C/[C@@H](O)C[C@@H](O)CC([O-])=O)C=C1.[Na+] | ||
| 分子式 | C26H33FNO5•Na | 分子量 | 481.5 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 10 mg/ml,Ethanol: 0.5 mg/ml,PBS (pH 7.2): 0.2 mg/ml | 储存条件 | Store at -20°C, stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0768 mL | 10.3842 mL | 20.7684 mL |
| 5 mM | 0.4154 mL | 2.0768 mL | 4.1537 mL |
| 10 mM | 0.2077 mL | 1.0384 mL | 2.0768 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Gateways to clinical trials
Methods Find Exp Clin Pharmacol 2004 Mar;26(2):129-61.PMID:15071612doi
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity(R), the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Activated protein C concentrate, Ad-CD154, Adeno-Interferon gamma, alemtuzumab, APC-8024, 9-aminocamptothecin, aprepitant, l-arginine hydrochloride, aripiprazole, arsenic trioxide, asimadoline; O6-Benzylguanine, bevacizumab, Bi-20, binodenoson, biphasic insulin aspart, bivatuzumab, 186Re-bivatuzumab, BMS-181176, bosentan, botulinum toxin type B, BQ-123, bryostatin 1; Carboxy- amidotriazole, caspofungin acetate, CB-1954, CC-4047, CDP-860, Cerivastatin sodium, clevidipine, CTL-102; 3,4-DAP, darbepoetin alfa, decitabine, desloratadine, DHA-paclitaxel, duloxetine hydrochloride; Efalizumab, EGF vaccine, eletriptan, eniluracil, ENMD-0997, eplerenone, eplivanserin, erlosamide, ertapenem sodium, escitalopram oxalate, esomeprazole magnesium, eszopiclone, everolimus, exatecan mesilate, exenatide, ezetimibe; Fondaparinux sodium, FR-901228, FTY-720; Gefitinib, gemtuzumab ozogamicin, gepirone hydrochloride; Hexyl insulin M2, human insulin; Imatinib mesylate, insulin detemir, insulin glargine, iodine (I131) tositumomab, ISV-205, ivabradine hydrochloride, ixabepilone; Levetiracetam, levocetirizine, linezolid, liposomal NDDP, lonafarnib, lopinavir, LY-156735; Mafosfamide cyclohexylamine salt, magnesium sulfate, maxacalcitol, meclinertant, melagatran, melatonin, MENT, mepolizumab, micafungin sodium, midostaurin, motexafin gadolinium; Nesiritide, NS-1209, NSC-601316, NSC-683864; Osanetant; Palonosetron hydrochloride, parecoxib sodium, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, pegylated OB protein, pemetrexed disodium, perillyl alcohol, picoplatin, pimecrolimus, pixantrone maleate, plevitrexed, polyglutamate paclitaxel, posurdex, pramlintide acetate, prasterone, pregabalin; Rasburicase, rimonabant hydrochloride, rostaporfin, rosuvastatin calcium; SDZ-SID-791, sibrotuzumab, sorafenib, SU-11248; Tadalafil, targinine, tegaserod maleate, telithromycin, TheraCIM, tigecycline, tiotropium bromide, tipifarnib, tirapazamine, treprostinil sodium; Valdecoxib, Valganciclovir hydrochloride, Vardenafil hydrochloride hydrate; Ximelagatran; Zofenopril calcium, Zoledronic acid monohydrate.
Selected Statins as Dual Antiproliferative-Antiinflammatory Compounds
Asian Pac J Cancer Prev 2022 Dec 1;23(12):4047-4062.PMID:36579985DOI:10.31557/APJCP.2022.23.12.4047.
Background: We hypothesized that superlative dual cytotoxicity-antiinflammtion bioefficacies of 9 selected lipophilic statins correlate to their chelation effect of 3,5-dihydroxyheptanoic acid.
Methodology: Lipophilic-acid chelating statins have been screened for in vitro duality of proliferation inhibition and NO-radical scavenging capacities.
Results: Their spectrum of selectivity indices for safety in PDL fibroblasts -based 72h incubations was reported. Surprisingly despite its lack on macrophages LPS-triggered inflammation over 5-200 µM and unlike the 8 statins; Cerivastatin had growth inhibition IC50 values of 40nM (SW620), 110nM (HT29), 2.9 µM (HCT116), 6µM (SW480), and most notably 38µM (<50 µM, in Caco2). Exclusively Cerivastatin exerted antitumorigenesis IC50 values <50 µM in all T47D, MCF7 and PANC1 72h cultures. In statins with greater antiinflammation affinity than indomethacin's; lovastatin had cytotoxicity IC50 values <20 µM in SW620
Cerivastatin: pharmacology of a novel synthetic and highly active HMG-CoA reductase inhibitor
Atherosclerosis 1997 Nov;135(1):119-30.PMID:9395280DOI:10.1016/s0021-9150(97)00188-3.
The pyridine derivative Cerivastatin is a new entirely synthetic and enantiomerically pure inhibitor of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase. As a sodium salt Cerivastatin is present in the active, open ring form. Cerivastatin inhibited the membrane-bound (non-solubilized) HMG-CoA reductase of the native microsomal fraction isolated from rat liver with a Ki value of 1.3 x 10(-9) M. The reference compound lovastatin was 100-fold less potent and exhibited a Ki value of 150 x 10(-9) M. Cerivastatin inhibited the cholesterol synthesis in the human hepatoma cell line HepG2 cells with a similar IC50 value of 1.0 x 10(-9) M. In vivo studies reflected its high in vitro activity. In both rats and dogs, Cerivastatin inhibited the hepatic [14C]cholesterol synthesis from [14C]acetate with an oral ED50 value of 0.002 mg/kg body weight, while lovastatin exhibited an oral ED50 value of 0.3 mg/kg in rats, showing again the ratio of 100 or more between Cerivastatin and lovastatin. In the small intestine and testes, Cerivastatin was at least 50-fold less active with oral ED50 values higher than 0.1 mg/kg, which is indicative for a high liver selectivity of Cerivastatin. In cholestyramine-primed dogs Cerivastatin dose-dependently lowered the serum cholesterol concentrations by up to 59% with 0.1 mg/kg after 20 days. Interestingly, the serum triglycerides were markedly reduced by 53 and 76% with 0.03 and 0.1 mg/kg, respectively. In normal chow fed dogs the low density lipoprotein (LDL) concentrations were reduced by up to 75% after 0.1 mg Cerivastatin/kg. The ratio of HDL/LDL increased by 81% compared with a change of only 14% in the placebo treated control group. The antiatherogenic effect of Cerivastatin was shown in rabbits fed a diet enriched with 0.2% cholesterol. After 9 weeks on diet 0.1 mg Cerivastatin/kg decreased the accumulation of cholesterol ester in the arterial tissue by 73%. In summary, these data as compared to published data on other HMG-CoA reductase inhibitors demonstrate Cerivastatin to be the most active compound in this class. Vastatins used in therapy are effective in mg doses, while Cerivastatin offers a new low dose therapy in the microg range.
The Guinea pig as a preclinical model for demonstrating the efficacy and safety of statins
J Pharmacol Exp Ther 2008 Feb;324(2):576-86.PMID:17986646DOI:10.1124/jpet.107.131615.
Statins, because of their excellent efficacy and manageable safety profile, represent a key component in the current armamentarium for the treatment of hypercholesterolemia. Nonetheless, myopathy remains a safety concern for this important drug class. Cerivastatin was withdrawn from the market for myotoxicity safety concerns. BMS-423526 [{(3R,5S)-7-[4-(4-fluorophenyl)-6,7-dihydro-2-(1-methylethyl)-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-3-yl]-3,5-dihydroxy-heptenoic acid} sodium salt], similar to Cerivastatin in potency and lipophilicity, was terminated in early clinical development due to an unacceptable myotoxicity profile. In this report, we describe the guinea pig as a model of statin-induced cholesterol lowering and myotoxicity and show that this model can distinguish statins with unacceptable myotoxicity profiles from statins with acceptable safety profiles. In our guinea pig model, both Cerivastatin and BMS-423526 induced myotoxicity at doses near the ED(50) for total cholesterol (TC) lowering in plasma. In contrast, wide differences between myotoxic and TC-lowering doses were established for the currently marketed, more hydrophilic statins, pravastatin, rosuvastatin, and atorvastatin. This in vivo model compared favorably to an in vitro model, which used statin inhibition of cholesterol synthesis in rat hepatocytes and L6 myoblasts as surrogates of potential efficacy and toxicity, respectively. Our conclusion is that the guinea pig is a useful preclinical in vivo model for demonstrating whether a statin is likely to have an acceptable therapeutic safety margin.
Is the Protein-Mediated Uptake of Drugs by Organic Anion Transporting Polypeptides a Real Phenomenon or an Artifact?
Drug Metab Dispos 2022 Sep;50(9):1132-1141.PMID:35351775DOI:10.1124/dmd.122.000849.
Plasma proteins or human serum albumin (HSA) have been reported to increase the in vitro intrinsic uptake clearance (CLint,uptake) of drugs by hepatocytes or organic anion transporting polypeptide (OATP)-transfected cell lines. This so-called protein-mediated uptake effect (PMUE) is thought to be due to an interaction between the drug-protein complex and the cell membrane causing an increase in the unbound drug concentration at the cell surface, resulting in an increase in the apparent CLint,uptake of the drug. To determine if the PMUE on OATP-mediated drug uptake is an artifact or a real phenomenon, we determined the effect of 1%, 2%, and 5% HSA on OATP1B1-mediated [human embryonic kidney (HEK)293 transfected cells] and passive CLint,uptake (mock HEK293 cells) on a cocktail of five statins. In addition, we determined the non-specific binding (NSB) of the statin-HSA complex to the cells/labware. The increase in uptake of atorvastatin, fluvastatin, and rosuvastatin in the presence of HSA was completely explained by the extent of NSB of the statin-HSA complex, indicating that the PMUE for these statins is an artifact. In contrast, this was not the case for OATP1B1-mediated uptake of pitavastatin and passive uptake of Cerivastatin, suggesting that the PMUE is a real phenomenon for these drugs. Additionally, the PMUE on OATP1B1-mediated uptake of pitavastatin was confirmed by a decrease in its unbound IC50 in the presence of 5% HSA versus Hank's balanced salt solution buffer (HBSS). These data question the utility of routinely including plasma proteins or HSA in uptake experiments and the previous findings on PMUE on OATP-mediated drug uptake. SIGNIFICANCE STATEMENT: Here we report, for the first time, that the protein-mediated uptake effect (PMUE) on organic anion transporting polypeptide (OATP)-transported drugs could be an artifact of the non-specific binding (NSB) of the drug-albumin complex to cells/labware. Future experiments on PMUE must take into consideration such NSB. In addition, mechanisms other than PMUE need to be explored to explain the underprediction of in vivo OATP-mediated hepatic drug clearance from in vitro uptake studies.