Simvastatin

Alias: MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin;
Cat No.:V0924 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 andcompetitive 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 Chemical Structure CAS No.: 79902-63-9
Product category: HMG-CoA Reductase
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
10mg
50mg
100mg
250mg
500mg
1g
2g
Other Sizes

Other Forms of Simvastatin:

  • Simvastatin-d6 (MK 733-d6)
  • Simvastatin-d11 (MK 733-d11)
  • Simvastatin-d3 (MK 733-d3)
Official Supplier of:
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Alternate Text
Top Publications Citing lnvivochem Products
Purity & Quality Control Documentation

Purity: ≥98%

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
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].
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].
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.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C25H38O5
Molecular Weight
418.57
CAS #
79902-63-9
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
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
Synonyms
MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin;
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)
Solubility Data
Solubility (In Vitro)
DMSO: 83 mg/mL (198.3 mM)
Water:<1 mg/mL
Ethanol:83 mg/mL (198.3 mM)
Solubility (In Vivo)
2% DMSO+30% PEG 300+5% Tween80+ddH2O:10 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
/

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
+
+
+

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.

Biological Data
  • Simvastatin

    Macromolecular synthesis in the presence of simvastatin.Sci Rep. 2015; 5: 16407.
  • Simvastatin

    Quantitative proteome analysis of S. aureus cells treated with simvastatin reveals extensive protein degradation.Sci Rep. 2015; 5: 16407.
  • Simvastatin

    Simvastatin inhibits bacterial protein synthesis and toxin production.Sci Rep. 2015; 5: 16407.
  • Simvastatin

    The effects of simvastatin and antibiotics (linezolid and vancomycin) on established biofilms of S. aureus (a) or S. epidermidis (b) were evaluated.Sci Rep. 2015; 5: 16407.
  • Simvastatin

    Antibacterial and anti-inflammatory activities of simvastatin in a mouse model of MRSA skin infection.Sci Rep. 2015; 5: 16407.
  • Simvastatin

    Synergistic activity of simvastatin with topical antimicrobials.Sci Rep. 2015; 5: 16407.
Contact Us