Hmdb loader
Survey
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version5.0
StatusDetected and Quantified
Creation Date2006-10-16 12:27:59 UTC
Update Date2022-03-07 02:49:25 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
Data?1582752339
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
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
Ontology
Physiological effectNot Available
Disposition
Process
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point135 - 138 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.012 g/LNot Available
LogP4.68HANSCH,C ET AL. (1995)
Experimental Chromatographic PropertiesNot Available
Predicted Molecular 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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+202.85131661259
DarkChem[M-H]-199.44431661259
DeepCCS[M-2H]-244.36230932474
DeepCCS[M+Na]+219.03530932474
AllCCS[M+H]+205.432859911
AllCCS[M+H-H2O]+203.132859911
AllCCS[M+NH4]+207.532859911
AllCCS[M+Na]+208.132859911
AllCCS[M-H]-205.632859911
AllCCS[M+Na-2H]-207.132859911
AllCCS[M+HCOO]-208.932859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Simvastatin[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)CC3779.9Standard polar33892256
Simvastatin[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)CC2909.0Standard non polar33892256
Simvastatin[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)CC3142.3Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Simvastatin,1TMS,isomer #1CCC(C)(C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O[Si](C)(C)C)CC(=O)O3)[C@H]212994.3Semi standard non polar33892256
Simvastatin,1TBDMS,isomer #1CCC(C)(C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O[Si](C)(C)C(C)(C)C)CC(=O)O3)[C@H]213225.0Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Simvastatin GC-MS (Non-derivatized) - 70eV, Positivesplash10-0fk9-9154200000-9a8f0d47976b67e5c9d52017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Simvastatin GC-MS (1 TMS) - 70eV, Positivesplash10-00b9-9137500000-2fdfacbca82ff764afb22017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Simvastatin GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
MSMass Spectrum (Electron Ionization)splash10-0a4i-3900000000-d04758924bf88a90c0172014-09-20Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-qTof , Positive-QTOFsplash10-0229-0967000000-6c51c479e90818ec703b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-qTof , Positive-QTOFsplash10-0229-0967000000-6c51c479e90818ec703b2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QTOF , positive-QTOFsplash10-0fya-0988400000-d9778b2f11696b81fb072017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QTOF , positive-QTOFsplash10-006w-0790000000-4f23e0376d85845e09642017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QTOF , positive-QTOFsplash10-05i1-0940000000-058f6298af54c05532ed2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QTOF , positive-QTOFsplash10-0092-0910000000-6ecd838b2f6fddf67dad2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QTOF , positive-QTOFsplash10-0597-0900000000-012d0d6fcabbd21d696d2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-000e-0590000000-7f99e0b9531d4f42831a2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-0092-1960000000-e8429bbec985c5ecdd2d2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-0592-1910000000-dc09a51ca37fe4d24a5a2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-0abd-1900000000-9b55821f49270e5dd5982017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-0536-1900000000-d8a41a97ccbdb30e5a5e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin LC-ESI-QFT , positive-QTOFsplash10-002f-2900000000-abe04d7f99c3eb0f2fcb2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 60V, Positive-QTOFsplash10-0abd-1900000000-78fbdab0700c9c2d0ea42021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 45V, Positive-QTOFsplash10-0592-1910000000-88e71bd3ee3ad70a99d12021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 50V, Positive-QTOFsplash10-0597-0900000000-093875a17b3bb042dc1b2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 40V, Positive-QTOFsplash10-0092-0910000000-6ecd838b2f6fddf67dad2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 30V, Positive-QTOFsplash10-05i1-0940000000-058f6298af54c05532ed2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Simvastatin 10V, Positive-QTOFsplash10-0fya-0988400000-d9778b2f11696b81fb072021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 10V, Positive-QTOFsplash10-0uxr-3028900000-ac9ec6a75c0ccc8028082016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 20V, Positive-QTOFsplash10-0fr2-9156100000-30ee09c0a70d4a8c7b202016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 40V, Positive-QTOFsplash10-00kb-9120000000-4cb8e77d058b47cb3d822016-06-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 10V, Negative-QTOFsplash10-014i-0009500000-4449db04da972dd8d05f2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 20V, Negative-QTOFsplash10-01dj-4109100000-a14d60d17f23d1fb98722016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Simvastatin 40V, Negative-QTOFsplash10-0006-9131000000-24b3e278d457c517b4142016-08-03Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue Locations
  • Skeletal Muscle
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.044 +/- 0.011 uMAdult (>18 years old)BothNormal details
BloodDetected but not QuantifiedNot QuantifiedAdult (>18 years old)BothNormal details
UrineDetected but not QuantifiedNot QuantifiedAdult (>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
FooDB 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
Food Biomarker OntologyNot Available
VMH IDSMV
MarkerDB IDNot Available
Good Scents IDNot Available
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.