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Record Information
Version1.0
Creation Date2014-09-11 05:16:36 UTC
Update Date2016-11-09 01:09:12 UTC
Accession NumberCHEM003745
Identification
Common NameSimvastatin
ClassSmall Molecule
DescriptionSimvastatin 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
Thumb
Synonyms
ValueSource
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-oneChEBI
MK-733ChEBI
SimvastatinaChEBI
SimvastatineChEBI
SimvastatinumChEBI
ZocorChEBI
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-oneGenerator
(+)-SimvastatinHMDB
CholestatHMDB
DenanHMDB
EucorHMDB
KolestevanHMDB
LipexHMDB
LipinormHMDB
LiponormHMDB
LipovasHMDB
LodalesHMDB
ModutrolHMDB
Nor-vastinaHMDB
PepstatinHMDB
RecholHMDB
SimcorHMDB
SimovilHMDB
Simvastatin lactoneHMDB
SimvotinHMDB
SinvacorHMDB
SinvascorHMDB
SivastinHMDB
StatinHMDB
SynvinolinHMDB
ValemiaHMDB
VelostatinHMDB
ZocordHMDB
Chemical FormulaC25H38O5
Average Molecular Mass418.566 g/mol
Monoisotopic Mass418.272 g/mol
CAS Registry Number79902-63-9
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 Namesimvastatin
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 IdentifierInChI=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 KeyRYMZZMVNJRMUDD-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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactones
Sub ClassDelta valerolactones
Direct ParentDelta 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 FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Muscle
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point135-138°C
Boiling PointNot Available
SolubilityInsoluble
Predicted Properties
PropertyValueSource
Water Solubility0.012 g/LALOGPS
logP4.51ALOGPS
logP4.46ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)14.91ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.83 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity117.68 m³·mol⁻¹ChemAxon
Polarizability47.85 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSsplash10-0fk9-9154200000-9a8f0d47976b67e5c9d5View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS)splash10-00b9-9137500000-2fdfacbca82ff764afb2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0229-0967000000-6c51c479e90818ec703bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0229-0967000000-6c51c479e90818ec703bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fya-0988400000-d9778b2f11696b81fb07View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-006w-0790000000-4f23e0376d85845e0964View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05i1-0940000000-058f6298af54c05532edView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0092-0910000000-6ecd838b2f6fddf67dadView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0597-0900000000-012d0d6fcabbd21d696dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000e-0590000000-7f99e0b9531d4f42831aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0092-1960000000-e8429bbec985c5ecdd2dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0592-1910000000-dc09a51ca37fe4d24a5aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0abd-1900000000-9b55821f49270e5dd598View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0536-1900000000-d8a41a97ccbdb30e5a5eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-002f-2900000000-abe04d7f99c3eb0f2fcbView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0uxr-3028900000-ac9ec6a75c0ccc802808View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fr2-9156100000-30ee09c0a70d4a8c7b20View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00kb-9120000000-4cb8e77d058b47cb3d82View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009500000-4449db04da972dd8d05fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01dj-4109100000-a14d60d17f23d1fb9872View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9131000000-24b3e278d457c517b414View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0a4i-3900000000-d04758924bf88a90c017View in MoNA
Toxicity Profile
Route of ExposureAbsorption 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 ToxicitySimvastatin 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.
MetabolismHepatic, 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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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 LevelNot Available
Health EffectsThe most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00641
HMDB IDHMDB0005007
FooDB IDFDB023580
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN ID2443
PDB IDNot Available
Wikipedia LinkSimvastatin
Chemspider ID49179
ChEBI ID9150
PubChem Compound ID54454
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot 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.

MSDSLink
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.
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=11336576
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=12827636
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=14561068
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=14973129
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=18199328
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=18688862
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=18936176