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Lovastatin (CHEM003744)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (10)XML
Record Information
Version1.0
Creation Date2014-09-11 05:16:33 UTC
Update Date2016-11-09 01:09:12 UTC
Accession NumberCHEM003744
Identification
Common NameLovastatin
ClassSmall Molecule
DescriptionLovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6' position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Anticholesteremic Agent
  • Drug
  • Ester
  • Ether
  • Hydroxymethylglutaryl-CoA Reductase Inhibitor
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(1S,3R,7S,8S,8AR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrateChEBI
2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactoneChEBI
6alpha-MethylcompactinChEBI
MevacorChEBI
MevinolinChEBI
MK-803ChEBI
ML-530bChEBI
(1S,3R,7S,8S,8AR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyric acidGenerator
2b,6a-Dimethyl-8a-(2-methyl-1-oxobutoxy)-mevinate lactoneGenerator
2b,6a-Dimethyl-8a-(2-methyl-1-oxobutoxy)-mevinic acid lactoneGenerator
2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinate lactoneGenerator
2Β,6α-dimethyl-8α-(2-methyl-1-oxobutoxy)-mevinate lactoneGenerator
2Β,6α-dimethyl-8α-(2-methyl-1-oxobutoxy)-mevinic acid lactoneGenerator
6a-MethylcompactinGenerator
6Α-methylcompactinGenerator
6 alpha-MethylcompactinHMDB
1 alpha-Isomer lovastatinHMDB
6 MethylcompactinHMDB
6-MethylcompactinHMDB
Lovastatin, 1 alpha-isomerHMDB
alpha-Isomer lovastatin, 1HMDB
Lovastatin, (1 alpha(s*))-isomerHMDB
Lovastatin, 1 alpha isomerHMDB
Monacolin KHMDB
Chemical FormulaC24H36O5
Average Molecular Mass404.540 g/mol
Monoisotopic Mass404.256 g/mol
CAS Registry Number75330-75-5
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 (2S)-2-methylbutanoate
Traditional Namelovastatin
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@@H](C)CC
InChI IdentifierInChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1
InChI KeyPCZOHLXUXFIOCF-BXMDZJJMSA-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
  • 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
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Lovastatin PathwayNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point174.5°C
Boiling PointNot Available
Solubility0.0004 mg/mL
Predicted Properties
PropertyValueSource
Water Solubility0.024 g/LALOGPS
logP4.11ALOGPS
logP3.9ChemAxon
logS-4.2ALOGPS
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
Refractivity113.18 m³·mol⁻¹ChemAxon
Polarizability46.11 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-MSsplash10-0a4r-9155000000-825da9f6a87f5a59c1c2View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4i-2910000000-dc8caf3905a76d1dc259View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4j-1910000000-8aeacab386a420581150View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS)splash10-03di-9137500000-a125220abcd76ffa9a89View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4i-2910000000-dc8caf3905a76d1dc259View in MoNA
GC-MSGC-MS Spectrum - EI-Bsplash10-0a4j-1910000000-8aeacab386a420581150View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0049000000-86650e3e374df663aa35View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0049000000-86650e3e374df663aa35View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-017j-3981000000-8a9df18d5a3d8401a040View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0k9j-0392200000-046f8ecdd9105ec8f133View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fg2-0590000000-79f2e6dc3b230361fea3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0092-0970000000-029f3798d63ab95ed321View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0592-0930000000-85de8f33dd78ba45de36View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05fv-0910000000-7a730b8fcd91e3df5b8fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000e-0590000000-2206c97b74e146b3218dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0092-1960000000-6b3a14df210273b89f18View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0592-1910000000-38bd634327305fe325cfView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0abd-1900000000-e7dab133ffe03d435831View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0536-2900000000-12e639483c7d1a83da05View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-002f-2900000000-ed64daa9de830f1f3cb0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-2019200000-72562315d7aa45f51111View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f79-9176000000-32a60aba487dd125aab1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-9130000000-effc5ee7a79a5469060cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009500000-03828e23d026b9da8a74View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-100r-5219100000-bd7b9834593ecb989122View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9132000000-6ad0a599a6d123e8d3bbView in MoNA
Toxicity Profile
Route of ExposureStudies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.
Mechanism of ToxicityLovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the ‘_-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.
MetabolismLovastatin is hepatically metabolized in which the major active metabolites are the beta-hydroxyacid of lovastatin, the 6'-hydroxy derivative, and two additional metabolites. Route of Elimination: Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine. Half Life: 5.3 hours
Toxicity ValuesLD50>1000 mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDDB00227
HMDB IDHMDB0014372
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDC00000547
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB ID803
Wikipedia LinkLovastatin
Chemspider ID48085
ChEBI ID40303
PubChem Compound ID53232
Kegg Compound IDC07074
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Donald F. Gerson, Xinfa Xiao, “Process for the production of lovastatin using Coniothyrium fuckelii.” U.S. Patent US5409820, issued January, 1984.

MSDSLink
General References
1. Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6.
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=11375168
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=11389707
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=11483865
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=18642339
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=24093797
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=7720768