Simvastatin

Name: Simvastatin
Brand: Selleck Chemicals
SKU: S1792
Rating: 5 (21 reviews)

For research use only.

Catalog No.S1792 Synonyms: MK-0733

21 publications

Molecular Weight(MW): 418.57

Simvastatin is a competitive inhibitor of HMG-CoA reductase with K_i of 0.1-0.2 nM in cell-free assays.

Selleck's Simvastatin has been cited by 21 publications

Cancer Cell, 2019, 36(2):179-193

PubMed: 31378681 ( click the link to review the publication )

Cell, 2019, 36(2):179-193

PubMed: 28162770 ( click the link to review the publication )

JAMA Oncol, 2015, 10.1001/jamaoncol.2015.0829

PubMed: ( click the link to review the publication )

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

PubMed: 26181260 ( click the link to review the publication )

Sci Rep, 2020, 10(1):931

PubMed: 31969633 ( click the link to review the publication )

Acta Biomater, 2019, 90:324-336

PubMed: 30954623 ( click the link to review the publication )

Int J Oncol, 2019, 54(6):2054-2068

PubMed: 31081050 ( click the link to review the publication )

Contrast Media Mol Imaging, 2019, 2019:2538909

PubMed: 30863219 ( click the link to review the publication )

Cell Physiol Biochem, 2018, 46(2):618-632

PubMed: 29617679 ( click the link to review the publication )

Haematologica, 2018, 10.3324/haematol.2018.204701

PubMed: 30467206 ( click the link to review the publication )

J Cell Physiol, 2018, 233(1):186-200

PubMed: 28639275 ( click the link to review the publication )

J Cell Physiol, 2018, 10.1002/jcp.27651

PubMed: 30378099 ( click the link to review the publication )

FASEB J, 2017, 31(2):625-635

PubMed: 27811063 ( click the link to review the publication )

Prostate, 2017, 77(13):1303-1311

PubMed: 28762529 ( click the link to review the publication )

Eur J Pharmacol, 2017, 813:161-171

PubMed: 28826913 ( click the link to review the publication )

Leuk Res, 2017, 55:49-54

PubMed: 28122283 ( click the link to review the publication )

Nucl Med Biol, 2017, 46:25-31

PubMed: 27984781 ( click the link to review the publication )

Int J Clin Exp Pathol, 2017, 10(12):11480-11488

PubMed: ( click the link to review the publication )

Stem Cell Reports, 2017, 8(6):1617-1629

PubMed: 28552603 ( click the link to review the publication )

J Virol, 2016, 90(24):11181-11196

PubMed: 27707921 ( click the link to review the publication )

Antiviral Res, 2015, 120:140-6

PubMed: 26086883 ( click the link to review the publication )

Purity & Quality Control

Choose Selective HMG-CoA Reductase Inhibitors

Biological Activity

Description

Simvastatin is a competitive inhibitor of HMG-CoA reductase with K_i of 0.1-0.2 nM in cell-free assays.

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	Activity Description	PMID
rat liver hepatocytes	MYHGeY5kfGmxbjDhd5NigQ>?		NI\vfXg1KGh?	NYW1fnNSUW6qaXLpeIlwdiCxZjDjbI9t\XO2ZYLvcEB{gW62aHXzbZMhcW5icnH0JIxqfmW{IHjldIF1d2O7dHXzJIFnfGW{IESgbJJ{NCCLQ{WwQVEvOyCwTR?=	NGXGfJgyPzV4MEe4PC=>
rat L6 cells	NYH4[plkTnWwY4Tpc44h[XO\|YYm=			NYXMb3UyUW6qaXLpeIlwdiCxZjDjbI9t\XO2ZYLvcEB{gW62aHXzbZMhcW5icnH0JGw3KGOnbHzzJIF{e2W\|c3XkJIF{KGmwY3;ydI9z[XSrb36gc4YhYzF2Q23hZ4V1[XSnIHnueI8h[2ixbHXzeIVzd2xuIFnDOVA:OC5yMkeg{txO	NVW3XYU6OTh2MUKzNVc>
HepG2 cells	MkP2SpVv[3Srb36gZZN{[Xl?			Mmf3TY4hfmm2cn:gbY5pcWKrdH;yfUBi[3Srdnn0fUB4[XNiZY\hcJVifGWmIH;uJINpd2ync4Tldo9tKGKrb4P5cpRp\XOrczDpckBJ\XCJMjDj[YxteyxiSVO1NF0xNjB2IN88US=>	NYS4UHplOTR5NEGyOVg>
HEK293 cells	NXP1SllpTnWwY4Tpc44h[XO\|YYm=			NInTfYJKdmirYnn0bY9vKG:oIF;BWHAySjFiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gTGVMOjl\|IHPlcIx{KHW\|aX7nJIV{fHKjZHnvcE0yP2KndHGt[4x2[3W{b37p[IUhe3Wkc4TyZZRmNCCLQ{WwQVQvPCEQvF2=	NEjOTG0zOjV6N{m4Oi=>
human A549 cells	M2PvWGN6fG:2b4jpZ:Kh[XO\|YYm=		MUO3NkBp	MVnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDBOVQ6KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MU[uN{DPxE1?	NXrpV2ZGOjN3N{C1OFI>
human HS68 cells	MUfDfZRwfG:6aXRCpIF{e2G7			MmqzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTHM3QCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyPUK2MlQh\|ryP	NXvGdpN6OjN3N{C1OFI>
mouse MEF cells	M4[3NmN6fG:2b4jpZ:Kh[XO\|YYm=			NH:1XldEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBOTUZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3ME2zOk44KM7:TR?=	NVrtOXZEOjN3N{C1OFI>
RASMC cells	Mn3OSpVv[3Srb36gZZN{[Xl?	NWjLZppEOiEQvF2=	NVTTVFFVPzJiaB?=	NW\pdnN7UW6qaXLpeIlwdiCxZjDyZZQhTnSjc3WgbY4hWkGVTVOgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKFKjczDwdoVvgWyjdHnvckBifCB{IIXNJIFnfGW{IEeyJIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	Mn3SNlE5ODJ7NE[=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	Nrf2; PubMed: 27323826 Oncotarget 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 Cell Death Dis 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 Cell Death Dis 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 Cell Death Dis 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 Oncotarget 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 Oncotarget 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 Cell Death Dis 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 Oncotarget 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

References

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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 Download Simvastatin SDF

Molecular Weight	418.57
Formula	C₂₅H₃₈O₅
CAS No.	79902-63-9
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	MK-0733
Smiles	CCC(C)(C)C(=O)OC1CC(C)C=C2C=CC(C)C(CCC3CC(O)CC(=O)O3)C12

In vivo Formulation Calculator (Clear solution)

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

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mg/kg

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% DMSO+ % + % Tween 80+ % ddH₂O

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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 DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，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.

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-05-15)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
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
NCT03329118	Unknown status	Drug: SHR3824 Simvastatin	Type 2 Diabetes	Jiangsu HengRui Medicine Co. Ltd.	November 24 2017	Phase 1
NCT03660293	Completed	Drug: Atorvastatin\|Drug: Captopril\|Drug: L-carnitine	Diabetes Mellitus Type 1	Tanta University	April 1 2017	Not Applicable

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

Tel: +1-832-582-8158 Ext:3

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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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