Name: Simvastatin (MK-733)
Brand: Selleck Chemicals
SKU: S1792
Rating: 5 (79 reviews)

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Quality Control

Batch: Purity: 99.92%

99.92

Related Targets	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Other HMG-CoA Reductase Inhibitors	Mevastatin SR-12813 Clinofibrate Dihydrolanosterol 7-ketocholesterol Cerivastatin sodium

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description
rat liver hepatocytes	Function assay		4 h	Inhibition of cholesterol synthesis in rat liver hepatocytes after 4 hrs, IC50=1.3 nM
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
HepG2 cells	Function assay			In vitro inhibitory activity was evaluated on cholesterol biosynthesis in HepG2 cells, IC50=0.04 μM
HEK293 cells	Function assay			Inhibition of OATP1B1 (unknown origin) expressed in HEK293 cells using estradiol-17beta-glucuronide substrate, IC50=4.4 μM
human A549 cells	Cytotoxic assay		72 h	Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=16.3 μM
human HS68 cells	Cytotoxic assay			Cytotoxicity against human HS68 cells after 72 hrs by MTT assay, IC50=26.4 μM
mouse MEF cells	Cytotoxic assay			Cytotoxicity against mouse MEF cells after 72 hrs by MTT assay, IC50=36.7 μM
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
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	418.57	Formula	C₂₅H₃₈O₅	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	79902-63-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	MK 733			Smiles	CCC(C)(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C

Solubility

In vitro
Batch:

DMSO : 83 mg/mL (198.29 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 83 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	4.150mg/ml (9.91mM)	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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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

%DMSO+ %

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.

Mechanism of Action

Targets/IC₅₀/Ki	HMG-CoA reductase (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. This compound 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. This compound treatment leads to a dose-dependent increase in serine 473 phosphorylation of Akt within 30 minutes, with maximal phosphorylation occurring at 1.0 µM. It (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. This chemical displays anti-inﬂammatory effects in vitro. It (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. This compound (10 µM) suppresses cell-mediated macrophage TNF-γ release induced via cognate interactions by ~30%.
Kinase Assay	HMG-CoA reductase activity assay
Kinase 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 5 μL 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.
In vivo	Simvastatin orally administration inhibits the conversion of radiolabeled acetate to cholesterol with IC50 of 0.2 mg/kg. This compound (4 mg/day) orally administration for 13 weeks to rabbits fed an atherogenic cholesterol-rich diet, returns the cholesterol-induced increases in total cholesterol, LDL-cholesterol and HDL-cholesterol to normal level. This compound (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. This compound influences inflammation independent of its effect on plasma cholesterol level. In cynomolgus monkeys consumed an atherogenic diet, this compound (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, accompanied by a 2.1-fold increases in lesional smooth muscle cell and collagen content.
References	[1] https://pubmed.ncbi.nlm.nih.gov/3076125/ [2] https://pubmed.ncbi.nlm.nih.gov/10973320/ [3] https://pubmed.ncbi.nlm.nih.gov/12538717/ [4] https://pubmed.ncbi.nlm.nih.gov/2724674/ [5] https://pubmed.ncbi.nlm.nih.gov/2106347/ [6] https://pubmed.ncbi.nlm.nih.gov/12231565/ [7] https://pubmed.ncbi.nlm.nih.gov/10965989/

Applications

Methods	Biomarkers	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

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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Handling Instructions

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

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Frequently Asked Questions

Question 1:
Can you please advise if it has been tested effectively for in vivo use in mice? What solvent can be used to deliver this compound 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 it?

Answer:
This compound 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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Simvastatin (MK-733) HMG-CoA Reductase inhibitor

Chemical Structure

Molecular Weight: 418.57