Simvastatin

Catalog No.S1792 Batch:S179207

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Technical Data

Formula

C25H38O5

Molecular Weight 418.57 CAS No. 79902-63-9
Solubility (25°C)* In vitro DMSO 84 mg/mL (200.68 mM)
Ethanol 84 mg/mL (200.68 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
4.15mg/ml Taking the 1 mL working solution as an example, add 50 μL of 83 mg/ml clear DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween-80 to the above system, mix evenly to clarify it; Then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Simvastatin is a competitive inhibitor of HMG-CoA reductase with Ki of 0.1-0.2 nM in cell-free assays. Simvastatin induces ferroptosis, mitophagy, autophagy and apoptosis.
Targets
HMG-CoA reductase [1]
(Cell-free assay)
0.1-0.2 nM(Ki)
In vitro

Prior to use in cell assays, Simvastatin needs to be activated by NaOH in EtOH treatment. Simvastatin inhibits cholesterol synthesis in mouse L-M cell (fibroblast), rat H4II E cell (liver), and human Hep G2 cell (liver) with IC50 of 19.3 nM, 13.3 nM and 15.6 nM, respectively. [1]

Simvastatin treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM. Simvastatin (1.0 μM) enhances phosphorylation of the endogenous Akt substrate endothelial nitric oxide synthase (eNOS), inhibits serum-free media undergo apoptosis and accelerates vascular structure formation. [2]

Simvastatin displays anti-inflammatory effects in vitro. Simvastatin (10 μM) reduces anti-CD3/anti-CD28 antibody-stimulated proliferation of PB-derived mononuclear cells and synovial fluid cells from rheumatoid arthritis blood, as well as IFN-γ release. Simvastatin (10 μM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%. [3]

In vivo

Simvastatin orally administration inhibits the conversion of radiolabeled acetate to cholesterol with IC50 of 0.2 mg/kg. [1]

Simvastatin (4 mg/day) orally administration for 13 weeks to rabbits fed an atherogenci cholesterol-rich diet, returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level. [4]

Simvastatin (6 mg/kg) produces an increase in LDL receptor-dependent binding and increases the number of hepatic LDL receptors in rabbits fed a diet containing 0.25% cholesterol. [5]

Simvastatin influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, Simvastatin (20 mg/kg/day) induces a 1.3-fold less macrophage content in lesions, and 2-fold less vascular cell adhesion molecule-1, interleukin-1beta, and tissue factor expression, companied by a 2.1-fold increases in lesional smooth muscle cell and collagen content. [6]

Protocol (from reference)

Kinase Assay:

[7]

  • HMG-CoA reductase activity assay

    The total volume of each assay is 95 μL and the reaction mixture contained 10 μL of the inhibiting compound to be tested and 85 μL of the incubating buffer containing 2 mg/mL liver microsomes, 0.1 M KH2PO4, pH 7.2, 5.7 mM dithiothreitol, 10 mM glucose-6-phosphate, 2 U/mL glucose-6-phosphate dehydrogenase, 1 mM NADP, 10 μM miconazole. Control experiments are done without NADPH generating system. All samples are incubated 10 min at 37 ℃ before addition of 5μL of substrate (unlabelled and 14C-HMG-3-hydroxy-3-methyl glutaryl CoA, final concentration 50 μM, 2.5 nCi/nmole). After 30 min at 37 ℃, the reaction is stopped by adding 27 μL 1N HCl and 20 μL of unlabelled mevalonolactone (200 μg/assay). The conversion of mevalonic acid to lactone is performed at room temperature for 60 min.

Cell Assay:

[2]

  • Cell lines

    HUVECs

  • Concentrations

    1 μM

  • Incubation Time

    30 minutes

  • Method

    HUVECs were treated with simvastatin for 30 minutes.

Animal Study:

[2]

  • Animal Models

    Male Japanese white rabbits

  • Dosages

    2.5, 5, & 10 mg/kg

  • Administration

    Oral

Customer Product Validation

, , JAMA Oncol, 2015, 1(4):495-504.

Data from [Data independently produced by , , Haematologica, 2018, doi: 10.3324/haematol.2018.204701]

Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 46(2):618-632]

Data from [Data independently produced by , , J Cell Physiol, 2018, 233(1):186-200]

Selleck's Simvastatin has been cited by 65 publications

Neuronal γ-secretase regulates lipid metabolism, linking cholesterol to synaptic dysfunction in Alzheimer's disease [ Neuron, 2023, S0896-6273(23)00513-5] PubMed: 37543038
Caffeine Supplementation and FOXM1 Inhibition Enhance the Antitumor Effect of Statins in Neuroblastoma [ Cancer Res, 2023, 83(13):2248-2261] PubMed: 37057874
MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer [ Cell Death Dis, 2023, 14(4):234] PubMed: 37005437
NFYC-37 promotes tumor growth by activating the mevalonate pathway in bladder cancer [ Cell Rep, 2023, 42(8):112963] PubMed: 37561631
Mitotic perturbation is a key mechanism of action of decitabine in myeloid tumor treatment [ Cell Rep, 2023, 42(9):113098] PubMed: 37714156
Hypoxia-altered cholesterol homeostasis enhances the expression of interferon-stimulated genes upon SARS-CoV-2 infections in monocytes [ Front Immunol, 2023, 14:1121864] PubMed: 37377965
Inference of glioblastoma migration and proliferation rates using single time-point images [ Commun Biol, 2023, 6(1):402] PubMed: 37055469
Metformin and simvastatin synergistically suppress endothelin 1-induced hypoxia and angiogenesis in multiple cancer types [ Cancer Sci, 2023, 114(2):640-653] PubMed: 36156330
Activation of the mevalonate pathway in response to anti-cancer treatments drives glioblastoma recurrences through activation of Rac-1 [ bioRxiv, 2023, 2023.07.23.550205] PubMed: 37546917
SREBP activation contributes to fatty acid accumulations in necroptosis [ RSC Chem Biol, 2023, 4(4):310-322] PubMed: 37034406

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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