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Record Information
Version4.0
StatusDetected and Quantified
Creation Date2006-10-16 12:27:59 UTC
Update Date2018-05-19 21:51:14 UTC
HMDB IDHMDB0005007
Secondary Accession Numbers
  • HMDB0014779
  • HMDB05007
  • HMDB14779
Metabolite Identification
Common NameSimvastatin
DescriptionSimvastatin is a hypolipidemic drug belonging to the class of pharmaceuticals called 'statins'. It is used to control hypercholesterolemia (elevated cholesterol levels) and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus; Simvastatin is a powerful lipid-lowering drug that can decrease low density lipoprotein (LDL) levels by up to 50 percent. It is used in doses of 5 mg up to 80 mg. Higher doses (160 mg) have been found to be too toxic, while giving only minimal benefit in terms of lipid lowering. There is no real effect on HDL and triglyceride levels. Simvastatin (INN) is a hypolipidemic drug belonging to the class of pharmaceuticals called 'statins'. It is used to control hypercholesterolemia (elevated cholesterol levels) and to prevent cardiovascular disease. Simvastatin is a synthetic derivate of a fermentation product of Aspergillus terreus; The drug is the form of an inactive lactone that is hydrolized after ingestion to produce the active agent. It is a white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol; Ezetimibe/simvastatin is a combination product to lower lipids and marketed as Vytorin.
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 Weight418.5662
Monoisotopic Molecular Weight418.271924326
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
CAS Registry Number79902-63-9
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 KeyRYMZZMVNJRMUDD-HGQWONQESA-N
Chemical Taxonomy
DescriptionThis compound 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
  • Dicarboxylic acid or derivatives
  • Oxane
  • Fatty acyl
  • Carboxylic acid ester
  • Secondary alcohol
  • Carboxylic acid derivative
  • Oxacycle
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alcohol
  • Organic oxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Ontology
Disposition

Route of exposure:

Source:

Biological location:

Process

Naturally occurring process:

Role

Biological role:

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point135 - 138 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.012 g/LNot Available
LogP4.68HANSCH,C ET AL. (1995)
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-MS (Non-derivatized) - 70eV, Positivesplash10-0fk9-9154200000-9a8f0d47976b67e5c9d5View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00b9-9137500000-2fdfacbca82ff764afb2View 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
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
Tissue Locations
  • Muscle
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.044 +/- 0.011 uMAdult (>18 years old)BothNormal details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00641
Phenol Explorer Compound IDNot Available
FoodDB IDFDB023580
KNApSAcK IDNot Available
Chemspider ID49179
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkSimvastatin
METLIN ID2443
PubChem Compound54454
PDB IDNot Available
ChEBI ID9150
References
Synthesis ReferenceWillard, 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
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. 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. [PubMed:16634254 ]
  2. Antons KA, Williams CD, Baker SK, Phillips PS: Clinical perspectives of statin-induced rhabdomyolysis. Am J Med. 2006 May;119(5):400-9. [PubMed:16651050 ]
  3. 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. [PubMed:16864763 ]
  4. Finsterer J, Zuntner G: Rhabdomyolysis from Simvastatin triggered by infection and muscle exertion. South Med J. 2005 Aug;98(8):827-9. [PubMed:16144183 ]
  5. 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. [PubMed:16433891 ]
  6. 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. [PubMed:16442367 ]
  7. Hellinger FJ, Encinosa WE: Inappropriate drug combinations among privately insured patients with HIV disease. Med Care. 2005 Sep;43(9 Suppl):III53-62. [PubMed:16116309 ]
  8. 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. [PubMed:17640385 ]

Only showing the first 10 proteins. There are 24 proteins in total.

Enzymes

General function:
Involved in hydroxymethylglutaryl-CoA reductase (NADPH) activity
Specific function:
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
Gene Name:
HMGCR
Uniprot ID:
P04035
Molecular weight:
97475.155
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
General function:
Involved in receptor signaling protein serine/threonine kinase activity
Specific function:
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin. May be involved for left-right pattern formation during embryogenesis
Gene Name:
ACVR1
Uniprot ID:
Q04771
Molecular weight:
57152.4
General function:
Involved in MAP kinase activity
Specific function:
Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4)
Gene Name:
MAPK3
Uniprot ID:
P27361
Molecular weight:
43135.2
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
General function:
Involved in GTP binding
Specific function:
Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP- dependent manner, suggesting that the insertion does not completely abolish effector interaction
Gene Name:
RAC1
Uniprot ID:
P63000
Molecular weight:
21449.9
General function:
Involved in serine-type endopeptidase inhibitor activity
Specific function:
This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, and protein C. Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis
Gene Name:
SERPINE1
Uniprot ID:
P05121
Molecular weight:
45059.7
General function:
Involved in chemokine activity
Specific function:
Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis
Gene Name:
CCL2
Uniprot ID:
P13500
Molecular weight:
11024.9
General function:
Involved in GTP binding
Specific function:
Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP
Gene Name:
RHOA
Uniprot ID:
P61586
Molecular weight:
21767.9
General function:
Involved in tumor necrosis factor receptor binding
Specific function:
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation
Gene Name:
TNF
Uniprot ID:
P01375
Molecular weight:
25644.1

Only showing the first 10 proteins. There are 24 proteins in total.