Simvastatin

For research use only.

Catalog No.S1792 Synonyms: MK-0733

31 publications

Simvastatin Chemical Structure

CAS No. 79902-63-9

Simvastatin (MK-0733) 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.

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10mM (1mL in DMSO) USD 97 In stock
USD 97 In stock
USD 227 In stock
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Selleck's Simvastatin has been cited by 31 publications

Purity & Quality Control

Choose Selective HMG-CoA Reductase Inhibitors

Biological Activity

Description Simvastatin (MK-0733) 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]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
rat liver hepatocytes MXLGeY5kfGmxbjDhd5NigQ>? NEDoU2I1KGh? NU\PfWxKUW6qaXLpeIlwdiCxZjDjbI9t\XO2ZYLvcEB{gW62aHXzbZMhcW5icnH0JIxqfmW{IHjldIF1d2O7dHXzJIFnfGW{IESgbJJ{NCCLQ{WwQVEvOyCwTR?= NWf3U3lxOTd3NkC3PFg>
rat L6 cells MYjGeY5kfGmxbjDhd5NigQ>? NWmwNJFSUW6qaXLpeIlwdiCxZjDjbI9t\XO2ZYLvcEB{gW62aHXzbZMhcW5icnH0JGw3KGOnbHzzJIF{e2W|c3XkJIF{KGmwY3;ydI9z[XSrb36gc4YhYzF2Q23hZ4V1[XSnIHnueI8h[2ixbHXzeIVzd2xuIFnDOVA:OC5yMkeg{txO MkHkNVg1OTJ|MUe=
HepG2 cells MUXGeY5kfGmxbjDhd5NigQ>? NYL0dnRQUW5idnn0do8hcW6qaXLpeI9zgSCjY4Tpeol1gSC5YYOg[ZZidHWjdHXkJI9vKGOqb3zld5Rmem:uIHLpc5N6dnSqZYPpd{BqdiCKZYDHNkBk\WyuczygTWM2OD1yLkC0JO69VQ>? MWqxOFc1OTJ3OB?=
HEK293 cells Mki1SpVv[3Srb36gZZN{[Xl? MUDJcohq[mm2aX;uJI9nKE:DVGCxRlEhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iSFXLNlk{KGOnbHzzJJV{cW6pIHXzeJJi\GmxbD2xO4JmfGFvZ3z1Z5Vzd26rZHWgd5Vje3S{YYTlMEBKSzVyPUSuOEDPxE1? NFe1[20zOjV6N{m4Oi=>
human A549 cells MlftR5l1d3SxeHnjxsBie3OjeR?= MmLjO|IhcA>? Mom3R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUG2MlMh|ryP MnzpNlM2PzB3NEK=
human HS68 cells MoPwR5l1d3SxeHnjxsBie3OjeR?= Ml3vR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTHM3QCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUK2MlQh|ryP NFLIU3YzOzV5MEW0Ni=>
mouse MEF cells M17CcWN6fG:2b4jpZ:Kh[XO|YYm= M4XFRmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJG1GTiClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUO2Mlch|ryP NXvpPW9VOjN3N{C1OFI>
RASMC cells MWLGeY5kfGmxbjDhd5NigQ>? NGXw[lIzKM7:TR?= NWCxbnM5PzJiaB?= MkK0TY5pcWKrdHnvckBw\iC{YYSgSpRie2ViaX6gVmFUVUNiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJHJieyCycnXufYxifGmxbjDheEAzKHWPIHHmeIVzKDd{IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= MViyNVgxOjl2Nh?=

... Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot
Nrf2; 

PubMed: 27323826     


A. HCT116 cells were treated with 5 μM and 10 μM of simvastatin for 24 h. Nuclear fractions and cytoplasmic fractions were respectively analyzed by Western blotting for the detection of Nrf2 nuclear translocation Simvastatin increases the nuclear accumulation of Nrf2 in a dose-dependent manner. C. HT-29 cells were treated with the indicated concentrations of simvastatin for 24 h. Nuclear fractions and cytoplasmic fractions were respectively analyzed by Western blotting for the detection of Nrf2 nuclear translocation. Simvastatin increased the nuclear accumulation of Nrf2 in a dose-dependent manner. 

p-RB / Cyclin D1 / p21 / p27 / PCNA / CDC45 ; 

PubMed: 28300827     


Hep3B cells were treated with Simvastatin (5 or 10 μM) or Atorvastatin (20 or 40 μM) for 24 or 72 h, and cell extracts were analyzed by immunoblotting. The expression of MCM7, RB, p-RB, cyclin D1, PCNA and CDC45 were reduced and the expressions of p21 and p27 were increased.

AMPK / p-AMPK / P70S6 / p-P70S6 / LC3 / Atg7 ; 

PubMed: 28300827     


Hep3B cells were treated with 5 or 10 μM Simvastatin for 24 or 72 h, and then cell extracts were analyzed by immunoblotting with AMPK cell signaling or cell autophagy-related antibodies. 

Bcl-2 / PARP / Caspase-3 / Cleaved Caspase-3 ; 

PubMed: 28300827     


U2OS/SaOS2 and SiHa/C33A were treated with Simvastatin (2.5 or 5 μM) for 24 or 72 h, and then cell extracts were analyzed by immunoblotting with apoptosis-related antibodies

HMGCR ; 

PubMed: 26503475     


The effect of simvastatin on its target, HMGCR, was examined by Western blot analysis. Simvastatin treatment resulted in a dose-dependent decrease in expression of HMGCR protein in both cell lines.

27323826 28300827 26503475
Immunofluorescence
Nrf2; 

PubMed: 27323826     


B. HCT116 cells were treated with 10 μM simvastatin for 24 h. After treatment, cell was fixed and labeled with an anti-Nrf2 antibody, followed by a fluorescein isothiocyanate (FITC)-conjugated secondary antibody. The nuclei were visualized by DAPI staining. Simvastatin for 24 h increased the nuclear accumulation of Nrf2 protein from the cytoplasm to the nucleus by immunocytochemical analysis. D. HT-29 cells were treated with 10 μM simvastatin for 24 h. After treatment, cells were fixed and labeled with an anti-Nrf2 antibody, followed by an FITC-conjugated secondary antibody. The nuclei were visualized by DAPI staining. Simvastatin for 24 h increased the nuclear accumulation of Nrf2 protein from the cytoplasm to the nucleus by immunocytochemical analysis. The data represent three independent experiments. SV, simvastatin.

LC3A/B; 

PubMed: 28300827     


Hep3B cells were treated with serum starvation or 5 μM Simvastatin for 72 h. Cell monolayers were fixed and stained with LC3A/B, and immunofluorescence images were presented (Scale bars, 10 μm).

27323826 28300827
Growth inhibition assay
Cell viability; 

PubMed: 26503475     


Hey and SKOV3 cells were cultured for 24 h and then treated with varying concentrations of simvastatin in 96 well plates for 72 h. Cell proliferation was assessed by MTT assay.

26503475
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

Solubility (25°C)

In vitro DMSO 83 mg/mL (198.29 mM)
Ethanol 83 mg/mL (198.29 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+30% PEG 300+5% Tween80+ddH2O
For best results, use promptly after mixing. 		10mg/mL

* 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.

Chemical Information

Molecular Weight 418.57
Formula

C25H38O5
CAS No. 79902-63-9
Storage powder
in solvent
Synonyms MK-0733
Smiles CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

In vivo Formulation Calculator (Clear solution)

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04457089 Recruiting Drug: Simvastatin 40mg Recurrent Ovarian Cancer|Platinum-sensitive Ovarian Cancer Bobbie Jo Rimel MD|Cedars-Sinai Medical Center December 2020 Early Phase 1
NCT04676282 Not yet recruiting Other: Hypothetical Scenario Polypharmacy|Aging University of Michigan|Maastricht University|University of Iowa|Johns Hopkins University|Newcastle University|University of Sydney December 2020 --
NCT03571802 Unknown status Drug: Simvastatin Obesity|Hyperlipidemias National University Hospital Singapore September 1 2018 Phase 4
NCT03387670 Recruiting Drug: Simvastatin|Drug: Placebo Secondary Progressive Multiple Sclerosis (SPMS) University College London|University of Edinburgh|Queen Mary University of London|London School of Hygiene and Tropical Medicine|University of Leeds|The Leeds Teaching Hospitals NHS Trust|Imperial College Healthcare NHS Trust March 28 2018 Phase 3

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

  • Question 1:

    Can you please advise if Simvastatin has been tested effectively for in vivo use in mice? What solvent can be used to deliver Simvastatin in vivo?

  • Answer:

    This compound is an oral drug and a lot of studies report its use in mice. According to this paper (http://atvb.ahajournals.org/content/21/1/115.full), 0.5% Methyl-cellulose can be used as the vehicle.

  • Question 2:

    If any specific protocols exist for in vitro use, specifically any steps required to activate the compound?

  • Answer:

    This product is supplied in an inactive form and requires treatment with NaOH in EtOH followed by neutralization to pH 7.2 for activation. Please find the details from the following reference: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739764/.

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HMG-CoA Reductase Signaling Pathway Map
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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID