Simvastatin (MK 733)

Catalog No.S1792 Synonyms: MK-0733

For research use only.

Simvastatin (MK-0733, MK 733) 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.

Simvastatin (MK 733) Chemical Structure

CAS No. 79902-63-9

Selleck's Simvastatin (MK 733) has been cited by 46 publications

Purity & Quality Control

Choose Selective HMG-CoA Reductase Inhibitors

Biological Activity

Description Simvastatin (MK-0733, MK 733) 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.
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 Mne4SpVv[3Srb36gZZN{[Xl? MnPWOEBp MVLJcohq[mm2aX;uJI9nKGOqb3zld5Rmem:uIIP5cpRp\XOrczDpckBz[XRibHn2[ZIhcGWyYYTvZ5l1\XNiYX\0[ZIhPCCqcoOsJGlEPTB;MT6zJI5O MVexO|U3ODd6OB?=
rat L6 cells MWTGeY5kfGmxbjDhd5NigQ>? Mk\nTY5pcWKrdHnvckBw\iClaH;s[ZN1\XKxbDDzfY51cGW|aYOgbY4hemG2IFy2JINmdGy|IHHzd4V{e2WmIHHzJIlv[2:{cH;yZZRqd25ib3[gX|E1S12jY3X0ZZRmKGmwdH:gZ4hwdGW|dHXyc4wtKEmFNUC9NE4xOjdizszN M4r4b|E5PDF{M{G3
HepG2 cells NXy4PWtHTnWwY4Tpc44h[XO|YYm= MoruTY4hfmm2cn:gbY5pcWKrdH;yfUBi[3Srdnn0fUB4[XNiZY\hcJVifGWmIH;uJINpd2ync4Tldo9tKGKrb4P5cpRp\XOrczDpckBJ\XCJMjDj[YxteyxiSVO1NF0xNjB2IN88US=> MkjENVQ4PDF{NUi=
HEK293 cells M3jIcmZ2dmO2aX;uJIF{e2G7 M{DH[mlvcGmkaYTpc44hd2ZiT1HUVFFDOSBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMhfXOrbneg[ZN1emGmaX;sMVE4[mW2YT3ncJVkfXKxbnnk[UB{fWK|dILheIUtKEmFNUC9OE41KM7:TR?= M1zPdlIzPTh5OUi2
human A549 cells M4PUVmN6fG:2b4jpZ:Kh[XO|YYm= NYXm[pZPPzJiaB?= MmLOR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gRVU1QSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG|c3H5MEBKSzVyPUG2MlMh|ryP MUeyN|U4ODV2Mh?=
human HS68 cells NWrnN21pS3m2b4TvfIlkyqCjc4PhfS=> NGe0R5NEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJWzZ6IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUC9NlYvPCEQvF2= MXyyN|U4ODV2Mh?=
mouse MEF cells NEG0TWhEgXSxdH;4bYPDqGG|c3H5 MVPDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDNSWYh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1|Nj63JO69VQ>? M{\zSFI{PTdyNUSy
RASMC cells Mm\LSpVv[3Srb36gZZN{[Xl? NGnuT2czKM7:TR?= MX:3NkBp NGj4WIRKdmirYnn0bY9vKG:oIILheEBHfGG|ZTDpckBTSVOPQzDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hWmG|IIDy[Y56dGG2aX;uJIF1KDJidV2gZYZ1\XJiN{KgbJJ{KGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NU\YdXBVOjF6MEK5OFY>
Methods Test Index PMID
Western blot Nrf2 ; p-RB / Cyclin D1 / p21 / p27 / PCNA / CDC45 ; AMPK / p-AMPK / P70S6 / p-P70S6 / LC3 / Atg7 ; Bcl-2 / PARP / Caspase-3 / Cleaved Caspase-3 ; HMGCR 27323826 28300827 26503475
Immunofluorescence Nrf2 ; LC3A/B 27323826 28300827
Growth inhibition assay Cell viability 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 (from reference)

Solubility (25°C)

In vitro

DMSO 83 mg/mL
(198.29 mM)
Water Insoluble
Ethanol ''83 mg/mL

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.


* 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


CAS No. 79902-63-9
Storage 3 years -20°C powder
2 years -80°C in solvent
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)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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 January 25 2021 Early Phase 1
NCT04676282 Enrolling by invitation Other: Hypothetical Scenario Polypharmacy|Aging University of Michigan|Maastricht University|University of Iowa|Johns Hopkins University|Newcastle University|University of Sydney December 17 2020 --
NCT03571802 Unknown status Drug: Simvastatin Obesity|Hyperlipidemias National University Hospital Singapore September 1 2018 Phase 4

(data from, updated on 2021-09-06)

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.

Handling Instructions

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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?

This compound is an oral drug and a lot of studies report its use in mice. According to this paper (, 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?

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:

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