ContaminantDB: Lovastatin

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 05:16:33 UTC

Update Date

2026-03-26 18:35:15 UTC

Accession Number

CHEM003744

Identification

Common Name

Lovastatin

Class

Small Molecule

Description

Lovastatin 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

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
(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-butyrate	ChEBI
2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone	ChEBI
6alpha-Methylcompactin	ChEBI
Mevacor	ChEBI
Mevinolin	ChEBI
MK-803	ChEBI
ML-530b	ChEBI
(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 acid	Generator
2b,6a-Dimethyl-8a-(2-methyl-1-oxobutoxy)-mevinate lactone	Generator
2b,6a-Dimethyl-8a-(2-methyl-1-oxobutoxy)-mevinic acid lactone	Generator
2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinate lactone	Generator
2Β,6α-dimethyl-8α-(2-methyl-1-oxobutoxy)-mevinate lactone	Generator
2Β,6α-dimethyl-8α-(2-methyl-1-oxobutoxy)-mevinic acid lactone	Generator
6a-Methylcompactin	Generator
6Α-methylcompactin	Generator
6 alpha-Methylcompactin	HMDB
1 alpha-Isomer lovastatin	HMDB
6 Methylcompactin	HMDB
6-Methylcompactin	HMDB
Lovastatin, 1 alpha-isomer	HMDB
alpha-Isomer lovastatin, 1	HMDB
Lovastatin, (1 alpha(s*))-isomer	HMDB
Lovastatin, 1 alpha isomer	HMDB
Monacolin K	HMDB

Chemical Formula

C₂₄H₃₆O₅

Average Molecular Mass

404.540 g/mol

Monoisotopic Mass

404.256 g/mol

CAS Registry Number

75330-75-5

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 Name

lovastatin

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 Identifier

InChI=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 Key

PCZOHLXUXFIOCF-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.

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
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 Framework

Aliphatic heteropolycyclic compounds

External Descriptors

polyketide (CHEBI:40303 )
fatty acid ester (CHEBI:40303 )
delta-lactone (CHEBI:40303 )
carbobicyclic compound (CHEBI:40303 )
statin (naturally occurring) (CHEBI:40303 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Lovastatin Pathway	Not Available	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	174.5°C
Boiling Point	Not Available
Solubility	0.0004 mg/mL

Predicted Properties

Property	Value	Source
Water Solubility	0.024 g/L	ALOGPS
logP	4.11	ALOGPS
logP	3.9	ChemAxon
logS	-4.2	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	113.18 m³·mol⁻¹	ChemAxon
Polarizability	46.11 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
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4i-2910000000-dc8caf3905a76d1dc259	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4j-1910000000-8aeacab386a420581150	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4i-2910000000-dc8caf3905a76d1dc259	Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0a4j-1910000000-8aeacab386a420581150	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4r-9155000000-825da9f6a87f5a59c1c2	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-03di-9137500000-a125220abcd76ffa9a89	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	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	splash10-000i-0049000000-86650e3e374df663aa35	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-000i-0049000000-86650e3e374df663aa35	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-017j-3981000000-8a9df18d5a3d8401a040	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0k9j-0392200000-046f8ecdd9105ec8f133	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0fg2-0590000000-79f2e6dc3b230361fea3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0092-0970000000-029f3798d63ab95ed321	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0592-0930000000-85de8f33dd78ba45de36	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05fv-0910000000-7a730b8fcd91e3df5b8f	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000e-0590000000-2206c97b74e146b3218d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0092-1960000000-6b3a14df210273b89f18	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0592-1910000000-38bd634327305fe325cf	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0abd-1900000000-e7dab133ffe03d435831	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0536-2900000000-12e639483c7d1a83da05	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-002f-2900000000-ed64daa9de830f1f3cb0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0092-0960000000-cb24a6eb72478d051b37	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0k9j-0392200000-046f8ecdd9105ec8f133	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0597-0910000000-87327bc487bcb23a89f1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-000b-0590000000-c8c50c20a62e59420cf2	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-05fv-0910000000-d4c442d499341c3a56f4	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-052r-2019200000-72562315d7aa45f51111	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0f79-9176000000-32a60aba487dd125aab1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-052r-9130000000-effc5ee7a79a5469060c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0009500000-03828e23d026b9da8a74	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-100r-5219100000-bd7b9834593ecb989122	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9132000000-6ad0a599a6d123e8d3bb	Spectrum

Toxicity Profile

Route of Exposure

Studies 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 Toxicity

Lovastatin 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.

Metabolism

Lovastatin 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 Values

LD₅₀>1000 mg/kg (orally in mice)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

For 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 Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Concentrations

Not Available

External Links

DrugBank ID