Home Metabolism HMG-CoA Reductase inhibitor - Ferroptosis activator - Autophagy activator - Mitophagy activator - Apoptosis related activator Simvastatin For research use only.

Simvastatin

Synonyms: MK 733

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.

Simvastatin Chemical Structure

Simvastatin Chemical Structure

CAS No. 79902-63-9

Purity & Quality Control

Simvastatin Related Products

Signaling Pathway

HMG-CoA Reductase Signaling Pathways

HMG-CoA Reductase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
rat liver hepatocytes Function assay 4 h Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs, IC50=1.3 nM 17560788
rat L6 cells Function assay Inhibition of cholesterol synthesis in rat L6 cells assessed as incorporation of [14C]acetate into cholesterol, IC50=0.027 μM 18412317
HepG2 cells Function assay In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells, IC50=0.04 μM 14741258
HEK293 cells Function assay Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells using estradiol-17beta-glucuronide substrate, IC50=4.4 μM 22587986
human A549 cells Cytotoxic assay 72 h Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=16.3 μM 23570542
human HS68 cells Cytotoxic assay Cytotoxicity against human HS68 cells after 72 hrs by MTT assay, IC50=26.4 μM 23570542
mouse MEF cells Cytotoxic assay Cytotoxicity against mouse MEF cells after 72 hrs by MTT assay, IC50=36.7 μM 23570542
RASMC cells Function assay 2 μM 72 h Inhibition of rat Ftase in RASMC cells assessed as reduction in Ras prenylation at 2 uM after 72 hrs by Western blot analysis 21802946
Click to View More Cell Line Experimental Data

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
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]
Kinase Assay 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 Research Cell lines HUVECs
Concentrations 1 μM
Incubation Time 30 minutes
Method

HUVECs were treated with simvastatin for 30 minutes.
Experimental Result Images Methods Biomarkers Images 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
Immunofluorescence Nrf2 LC3A/B 27323826
Growth inhibition assay Cell viability 26503475
In Vivo
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]
Animal Research Animal Models Male Japanese white rabbits
Dosages 2.5, 5, & 10 mg/kg
Administration Oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05771675 Not yet recruiting
Recurrent Acute Pancreatitis|Chronic Pancreatitis
Cedars-Sinai Medical Center|United States Department of Defense
 January 2024 Early Phase 1
NCT05542095 Withdrawn
Olfactory Disorder|COVID-19
Washington University School of Medicine|Duke University
 May 1 2023 Phase 1
NCT06207682 Completed
Healthy Volunteers
Amgen
 June 28 2022 Phase 1

Chemical Information & Solubility

Molecular Weight 418.57 Formula

C25H38O5
CAS No. 79902-63-9 SDF Download Simvastatin SDF
Smiles CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 83 mg/mL ( (198.29 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 83 mg/mL

Water : Insoluble


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In vivo
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In vivo Formulation Calculator

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In vivo Formulation Calculator (Clear solution)

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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.

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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?

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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