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250mg |
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Purity: ≥98%
Simvastatin (MK0733, Zocor; Synvinolin; Sinvacor; MK-0733; SIM), a marketed anti-hyperlipidemic drug of the statin class, is a lactone prodrug that has to be activated through hydrolysis to the active β-hydroxy acid form, which then acts as a potent and competitive inhibitor of HMG-CoA (3-hydroxy-3-methyl glutaryl coenzyme A) reductase with Ki of 0.1-0.2 nM in cell-free assays. simvastatin has been used for the treatment of coronary heart disease, hyperlipidemia (often in combination with ezetimibe), atherosclerosis, hypercholesterolemia, and stroke. As a prodrug, simvastatin is biologically inactive, and has to be activated as aforementioned.
ln Vitro |
Simvastatin is an inactive medication precursor that needs to be broken down into its hydroxy acid form in the liver in order to start working. It has no drug activity of its own. Sodium hydroxide (NaOH) can activate it in in vitro tests. Simvastatin has IC50 values of 19.3 nM, 13.3 nM, and 15.6 nM, respectively, which inhibit the synthesis of cholesterol in mouse LM cells, rat H4II E cells, and human Hep G2 cells[1]. Within 30 minutes, simvastatin increases serine 473 phosphorylation of Akt in a dose-dependent manner; peak phosphorylation happens at 1.0 µM[2]. Simvastatin (1.0 μM) suppresses serum-free media undergo apoptosis, speeds up the creation of vascular structures, and increases phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS)[2]. Simvastatin has anti-inflammatory properties and decreases IFN-γ release at 10 μM, as well as the proliferation of PB-derived mononuclear cells and synovial fluorid cells from rheumatoid arthritis blood induced by anti-CD3/anti-CD28 antibodies[3]. Additionally, around 30% of cell-mediated macrophage TNF-γ release produced via cognate contacts is blocked by simvastatin (10 μM)[3]. In astrocytes and neuroblastoma cells, simvastatin (5 μM) dramatically decreases ABCA1 expression, apolipoprotein E expression in astrocytes, and enhances glycogen synthase kinase 3β and cyclin-dependent kinase 5 expression in SK-N-SH cells[7]. Exosome release can be inhibited by simvastatin[10]. Simvastatin slows tumor cell development and causes it to stop in the G0/G1 phase at 32 and 64 μM; 24, 48, and 72 hours[11]. In HepG2 and Huh7 cells, simvastatin (32 and 64 μM; 48 h) causes apoptosis[11].
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ln Vivo |
When administered po, simvastatin inhibits the conversion of radiolabeled acetate to cholesterol with an IC50 of 0.2 mg/kg[1]. In rabbits fed an atherogenci cholesterol-rich diet, simvastatin (4 mg/day, po for 13 weeks) reverses the increases in total cholesterol, LDL cholesterol, and HDL cholesterol to normal levels[4]. In rabbits fed a diet containing 0.25% cholesterol, simvastatin (6 mg/kg) increases the number of hepatic LDL receptors and LDL receptor-dependent binding[5]. In cynomolgus monkeys fed an atherogenic diet, simvastatin (20 mg/kg/day) causes a 1.3-fold decrease in macrophage content in lesions and a 2-fold decrease in vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression. These reductions are accompanied by a 2.1-fold increase in lesional smooth muscle cell and collagen content[6]. Treatment with simvastatin (oral gavage; once daily; 14 d); 15 and 30 mg/kg) reduces oxidative damage, TNF-a and IL-6 levels, and revives the activities of the mitochondrial enzyme complex[12].
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Cell Assay |
Cell Proliferation Assay[11]
Cell Types: HepG2 and Huh7 cells Tested Concentrations: 32 and 64 μM Incubation Duration: 24, 48, and 72 hrs (hours) Experimental Results: Inhibited tumor cell growth as compared to controls (ctrl, p<0.05). Apoptosis Analysis[11] Cell Types: HepG2 and Huh7 cells Tested Concentrations: 32 and 64 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased early apoptosis from 9.2% in non-treated ctrl cells to 18.2% (32 μM) and 19.8% (64 μM), respectively, increased late apoptosis from 35.0% in ctrl cells to 56.9% (32 μM) and 48.0% (64 μM), respectively, in HepG2 cells. Cell Cycle Analysis[11] Cell Types: HepG2 and Huh7 cells Tested Concentrations: 32 and 64 μM Incubation Duration: 24, 48, and 72 hrs (hours) Experimental Results: demonstrated downregulation of CDK1, CDK2, CDK4 and cyclins D1 and E as compared to ctrl tumor cells. |
Animal Protocol |
Animal/Disease Models: Male wistar rats with oxidative damage by Intrastriatal 6-OHDA administration[12]
Doses: 15 and 30 mg/kg Route of Administration: po (oral gavage); 15 and 30 mg/kg; one time/day; 14 days Experimental Results: Attenuated oxidative damage (decreased MDA, nitrite levels and restoration of decreased GSH), attenuated TNF-a and IL-6 levels, and restored itochondrial enzyme complex activities as compared to 6-OHDA group. |
References |
[1]. Slater, E.E., et al. Mechanism of action and biological profile of HMG CoA reductase inhibitors. A new therapeutic alternative. Drugs, 1988. 36 Suppl 3: p. 72-82.
[2]. Kureishi, Y., et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med, 2000. 6(9): p. 1004-10. [3]. Leung BP, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003 Feb 1;170(3):1524-30. [4]. Kobayashi M, et al. Preventive effect of MK-733 (simvastatin), an inhibitor of HMG-CoA reductase, on hypercholesterolemia and atherosclerosis induced by cholesterol feeding in rabbits. Jpn J Pharmacol. 1989 Jan;49(1):125-33. [5]. Ishida F, et al. Comparative effects of simvastatin (MK-733) and CS-514 on hypercholesterolemia induced by cholesterol feeding in rabbits. Biochim Biophys Acta. 1990 Feb 23;1042(3):365-73. [6]. Sukhova GK, et al. Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1452-8. [7]. Weijiang Dong, et al. Differential effects of simvastatin and CS-514 on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells. J Lipid Res. 2009 Oct; 50(10): 2095-2102. [8]. Liu Z, et al. Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat. Oxid Med Cell Longev. 2017;2017:3861914. [9]. Ifergan I, et al. Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol. 2006 Jul;60(1):45-55. [10]. Zhang H, et al. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020;35(1):1322-1330. [11]. Borna Relja, et al. Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells. Int J Mol Med. 2010 Nov;26(5):735-41. [12]. Anil Kumar, et al. Neuroprotective potential of atorvastatin and simvastatin (HMG-CoA reductase inhibitors) against 6-hydroxydopamine (6-OHDA) induced Parkinson-like symptoms. Brain Res. 2012 Aug 30;1471:13-22. |
Molecular Formula |
C25H38O5
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Molecular Weight |
418.57
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CAS # |
79902-63-9
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SMILES |
C[C@H]1C=CC2=C[C@H](C)C[C@H](OC(C(C)(C)CC)=O)C2[C@H]1CC[C@@H]3C[C@@H](O)CC(O3)=O
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Chemical Name |
(1S,3R,7S,8S)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate
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Synonyms |
MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin;
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.3891 mL | 11.9454 mL | 23.8909 mL | |
5 mM | 0.4778 mL | 2.3891 mL | 4.7782 mL | |
10 mM | 0.2389 mL | 1.1945 mL | 2.3891 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.