ContaminantDB: Simvastatin

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (10)XML

Record Information

Version

1.0

Creation Date

2014-09-11 05:16:36 UTC

Update Date

2026-03-31 17:16:21 UTC

Accession Number

CHEM003745

Identification

Common Name

Simvastatin

Class

Small Molecule

Description

Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol.

Contaminant Sources

FooDB Chemicals
STOFF IDENT Compounds
T3DB toxins
ToxCast & Tox21 Chemicals

Contaminant Type

Anticholesteremic Agent
Drug
Ester
Ether
Food Toxin
Fungal Toxin
Hydroxymethylglutaryl-CoA Reductase Inhibitor
Hypolipidemic Agent
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF 3D-SDF PDB SMILES InChI View 3D Structure

Synonyms

Value	Source
2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8ar)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one	ChEBI
MK-733	ChEBI
Simvastatina	ChEBI
Simvastatine	ChEBI
Simvastatinum	ChEBI
Zocor	ChEBI
2,2-Dimethylbutyrate, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8ar)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one	Generator
(+)-Simvastatin	HMDB
Cholestat	HMDB
Denan	HMDB
Eucor	HMDB
Kolestevan	HMDB
Lipex	HMDB
Lipinorm	HMDB
Liponorm	HMDB
Lipovas	HMDB
Lodales	HMDB
Modutrol	HMDB
Nor-vastina	HMDB
Pepstatin	HMDB
Rechol	HMDB
Simcor	HMDB
Simovil	HMDB
Simvastatin lactone	HMDB
Simvotin	HMDB
Sinvacor	HMDB
Sinvascor	HMDB
Sivastin	HMDB
Statin	HMDB
Synvinolin	HMDB
Valemia	HMDB
Velostatin	HMDB
Zocord	HMDB

Chemical Formula

C₂₅H₃₈O₅

Average Molecular Mass

418.566 g/mol

Monoisotopic Mass

418.272 g/mol

CAS Registry Number

79902-63-9

IUPAC Name

(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate

Traditional Name

simvastatin

SMILES

[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC

InChI Identifier

InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1

InChI Key

RYMZZMVNJRMUDD-HGQWONQESA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as delta valerolactones. These are cyclic organic compounds containing an oxan-2- one moiety.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Lactones

Sub Class

Delta valerolactones

Direct Parent

Delta valerolactones

Alternative Parents

Substituents

Delta_valerolactone
Fatty acid ester
Delta valerolactone
Fatty acyl
Oxane
Dicarboxylic acid or derivatives
Secondary alcohol
Carboxylic acid ester
Oxacycle
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Alcohol
Aliphatic heteropolycyclic compound

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

statin (semi-synthetic) (CHEBI:9150 )
fatty acid ester (CHEBI:9150 )
delta-lactone (CHEBI:9150 )
carbobicyclic compound (CHEBI:9150 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Muscle

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	135-138°C
Boiling Point	Not Available
Solubility	Insoluble

Predicted Properties

Property	Value	Source
Water Solubility	0.012 g/L	ALOGPS
logP	4.51	ALOGPS
logP	4.46	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Acidic)	14.91	ChemAxon
pKa (Strongest Basic)	-2.8	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	72.83 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	117.68 m³·mol⁻¹	ChemAxon
Polarizability	47.85 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0fk9-9154200000-9a8f0d47976b67e5c9d5	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-00b9-9137500000-2fdfacbca82ff764afb2	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0229-0967000000-6c51c479e90818ec703b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0229-0967000000-6c51c479e90818ec703b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0fya-0988400000-d9778b2f11696b81fb07	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-006w-0790000000-4f23e0376d85845e0964	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05i1-0940000000-058f6298af54c05532ed	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0092-0910000000-6ecd838b2f6fddf67dad	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0597-0900000000-012d0d6fcabbd21d696d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000e-0590000000-7f99e0b9531d4f42831a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0092-1960000000-e8429bbec985c5ecdd2d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0592-1910000000-dc09a51ca37fe4d24a5a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0abd-1900000000-9b55821f49270e5dd598	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0536-1900000000-d8a41a97ccbdb30e5a5e	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-002f-2900000000-abe04d7f99c3eb0f2fcb	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0abd-1900000000-78fbdab0700c9c2d0ea4	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-0592-1910000000-88e71bd3ee3ad70a99d1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0597-0900000000-093875a17b3bb042dc1b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0092-0910000000-6ecd838b2f6fddf67dad	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-05i1-0940000000-058f6298af54c05532ed	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0fya-0988400000-d9778b2f11696b81fb07	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0uxr-3028900000-ac9ec6a75c0ccc802808	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0fr2-9156100000-30ee09c0a70d4a8c7b20	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00kb-9120000000-4cb8e77d058b47cb3d82	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-0009500000-4449db04da972dd8d05f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01dj-4109100000-a14d60d17f23d1fb9872	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9131000000-24b3e278d457c517b414	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0a4i-3900000000-d04758924bf88a90c017	Spectrum

Toxicity Profile

Route of Exposure

Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues. However, because simvastatin undergoes extensive first-pass metabolism, the availability of the drug in the systemic is low. Peak plasma concentration occurs 1.3 - 2.4 hours after administration.

Mechanism of Toxicity

Simvastatin is a prodrug in which the 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.

Metabolism

Hepatic, simvastatin is a substrate for CYP3A4. The major active metabolites of simvastatin are ‘_-hydroxyacid metabolite and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives Route of Elimination: Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Half Life: 3 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It can also be used in adolescent patients for the treatment of heterozygous familial hypercholesterolemia.

Minimum Risk Level

Not Available

Health Effects

The most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).

Symptoms

Not Available

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID

DB00641

HMDB ID

HMDB0005007

FooDB ID

FDB023580

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

2443

PDB ID

Not Available

Wikipedia Link

Chemspider ID

ChEBI ID

PubChem Compound ID

Kegg Compound ID

Not Available

YMDB ID

Not Available

ECMDB ID

Not Available

References

Synthesis Reference

Shieh-Shung J. Chen, Byron H. Arison, “Process for the preparation of 3-keto, 5-hydroxy simvastatin analogs.” U.S. Patent US4965200, issued April, 1981.

MSDS

Link

General References

1. Willard, Alvin K.; Smith, Robert L.; Hoffman, William F. 6(R)-[2-(8-acyloxy-2-methyl-6-methyl (or hydrogen)-polyhydro-1-naphthyl)ethyl]-4(R)-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-ones, the hydroxy acid forms of these pyranones, salts and esters thereof, and a pharmaceutical antihypercholesterolemic composition containing them. Eur. Pat. Appl. (1981), 54 pp. CODEN: EPXXDW EP 33538 19810812 CAN 95:219968 AN 1981:619968

2. Mahboobi SK, Shohat EZ, Jellinek SP, Rose M: Systemic infections can decrease the threshold of statin-induced muscle injury. South Med J. 2006 Apr;99(4):403-4.

3. Antons KA, Williams CD, Baker SK, Phillips PS: Clinical perspectives of statin-induced rhabdomyolysis. Am J Med. 2006 May;119(5):400-9.

4. Tsivgoulis G, Spengos K, Karandreas N, Panas M, Kladi A, Manta P: Presymptomatic neuromuscular disorders disclosed following statin treatment. Arch Intern Med. 2006 Jul 24;166(14):1519-24.

5. Finsterer J, Zuntner G: Rhabdomyolysis from Simvastatin triggered by infection and muscle exertion. South Med J. 2005 Aug;98(8):827-9.

6. Soininen K, Niemi M, Kilkki E, Strandberg T, Kivisto KT: Muscle symptoms associated with statins: a series of twenty patients. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):51-4.

7. Davidson MH, Maccubbin D, Stepanavage M, Strony J, Musliner T: Striated muscle safety of ezetimibe/simvastatin (Vytorin). Am J Cardiol. 2006 Jan 15;97(2):223-8. Epub 2005 Nov 21.

8. Hellinger FJ, Encinosa WE: Inappropriate drug combinations among privately insured patients with HIV disease. Med Care. 2005 Sep;43(9 Suppl):III53-62.

9. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE: Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease. BMC Med. 2007 Jul 19;5:20.