Identification

Name
Lovastatin
Accession Number
DB00227  (APRD00370)
Type
Small Molecule
Groups
Approved, Investigational
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.

Structure
Thumb
Synonyms
  • (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
  • 2β,6α-dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone
  • 6-alpha-methylcompactin
  • 6alpha-methylcompactin
  • 6α-methylcompactin
  • Lovastatina
  • Lovastatine
  • Lovastatinum
  • Mevinolin
External IDs
L-154803 / MK-803 / ML-530B
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act LovastatinTablet40 mgOralActavis Pharma Company2004-07-28Not applicableCanada
Act LovastatinTablet20 mgOralActavis Pharma Company2004-07-28Not applicableCanada
AltoprevTablet, extended release60 mg/1OralPhysicians Total Care, Inc.2005-07-112012-06-30Us
AltoprevTablet, extended release20 mg/1OralCovis Pharma2016-05-01Not applicableUs
AltoprevTablet, extended release20 mg/1OralShionogi2002-06-262017-12-31Us
AltoprevTablet, extended release60 mg/1OralCovis Pharma2016-05-01Not applicableUs
AltoprevTablet, extended release60 mg/1OralShionogi2002-06-262016-12-31Us
AltoprevTablet, extended release40 mg/1OralPhysicians Total Care, Inc.2006-01-252011-06-30Us
AltoprevTablet, extended release40 mg/1OralCovis Pharma2016-05-01Not applicableUs
AltoprevTablet, extended release40 mg/1OralShionogi2002-06-262018-02-28Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-lovastatin - Tab 20mgTablet20 mgOralApotex Corporation1997-03-27Not applicableCanada
Apo-lovastatin - Tab 40mgTablet40 mgOralApotex Corporation1997-03-27Not applicableCanada
Ava-lovastatinTablet20 mgOralAvanstra Inc2011-08-182014-08-21Canada
Ava-lovastatinTablet40 mgOralAvanstra Inc2011-08-182014-08-21Canada
Dom-lovastatinTablet40 mgOralDominion Pharmacal2003-02-25Not applicableCanada
Dom-lovastatinTablet20 mgOralDominion Pharmacal2003-02-25Not applicableCanada
LovastatinTablet10 mg/1OralProficient Rx LP2002-11-25Not applicableUs
LovastatinTablet20 mg/1OralREMEDYREPACK INC.2013-01-032016-11-22Us
LovastatinTablet20 mg/1OralActavis Pharma, Inc.2001-12-17Not applicableUs45963 0634 01 nlmimage10 773dbbfd
LovastatinTablet40 mg/1OralInternational Laboratories, Llc2010-04-10Not applicableUs68180 0469 03 nlmimage10 3d089ee4
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AdvicorLovastatin (20 mg/1) + Niacin (500 mg/1)Tablet, extended releaseOralPhysicians Total Care, Inc.2003-06-03Not applicableUs
AdvicorLovastatin (20 mg) + Niacin (500 mg)Tablet, extended release; Tablet, multilayer, extended releaseOralSepracor Pharmaceuticals Inc2005-11-092012-08-02Canada
AdvicorLovastatin (20 mg/1) + Niacin (1000 mg/1)Tablet, extended releaseOralKos Pharmaceuticals, Inc.2007-02-202007-02-20Us
AdvicorLovastatin (20 mg/1) + Niacin (500 mg/1)Tablet, extended releaseOralKos Pharmaceuticals, Inc.2007-02-202007-02-20Us
AdvicorLovastatin (20 mg/1) + Niacin (750 mg/1)Tablet, extended releaseOralAbbvie2001-12-172017-04-30Us
AdvicorLovastatin (20 mg/1) + Niacin (1000 mg/1)Tablet, extended releaseOralPhysicians Total Care, Inc.2004-06-072012-06-30Us
AdvicorLovastatin (40 mg) + Niacin (1000 mg)Tablet, extended release; Tablet, multilayer, extended releaseOralSepracor Pharmaceuticals Inc2007-05-152010-07-26Canada
AdvicorLovastatin (40 mg/1) + Niacin (1000 mg/1)Tablet, extended releaseOralAbbvie2001-12-172018-01-31Us
AdvicorLovastatin (20 mg/1) + Niacin (500 mg/1)Tablet, extended releaseOralAbbvie2001-12-172018-03-31Us
AdvicorLovastatin (20 mg/1) + Niacin (750 mg/1)Tablet, extended releaseOralPhysicians Total Care, Inc.2004-02-182011-06-30Us
International/Other Brands
Altocor / Mevacor
Categories
UNII
9LHU78OQFD
CAS number
75330-75-5
Weight
Average: 404.5396
Monoisotopic: 404.256274262
Chemical Formula
C24H36O5
InChI Key
PCZOHLXUXFIOCF-BXMDZJJMSA-N
InChI
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
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
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

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

The primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Lovastatin lowers hepatic cholesterol synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.

Mechanism of action

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 β-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.

TargetActionsOrganism
A3-hydroxy-3-methylglutaryl-coenzyme A reductase
inhibitor
Human
NIntegrin alpha-L
other/unknown
Human
NHistone deacetylase 2
other
Human
Absorption

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.

Volume of distribution

Lovastatin is able to cross the blood-brain-barrier and placenta.

Protein binding

Lovastatin and its β-hydroxyacid metabolites are highly protein bound (>95%).

Metabolism

Lovastatin is hepatically metabolized in which the major active metabolites are the β-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

Clearance
Not Available
Toxicity

LD50>1000 mg/kg (orally in mice)

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Lovastatin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Lovastatin can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Lovastatin can be decreased when combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of Lovastatin can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lovastatin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Lovastatin.
5-androstenedioneThe metabolism of Lovastatin can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Lovastatin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Lovastatin can be decreased when combined with 6-O-benzylguanine.
AbemaciclibThe metabolism of Lovastatin can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Lovastatin can be decreased when combined with Abiraterone.
Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking with grapefruit juice.
  • Take with food, 50% increase in bioavailability when taken with food.

References

Synthesis Reference

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

US5409820
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. [PubMed:9583372]
External Links
Human Metabolome Database
HMDB0014372
KEGG Drug
D00359
KEGG Compound
C07074
PubChem Compound
53232
PubChem Substance
46508223
ChemSpider
48085
BindingDB
34168
ChEBI
40303
ChEMBL
CHEMBL503
Therapeutic Targets Database
DAP000551
PharmGKB
PA450272
IUPHAR
2739
Guide to Pharmacology
GtP Drug Page
HET
803
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lovastatin
ATC Codes
C10BA01 — Lovastatin and nicotinic acidC10AA02 — Lovastatin
AHFS Codes
  • 24:06.08 — Hmg-coa Reductase Inhibitors
PDB Entries
1cqp
FDA label
Download (126 KB)
MSDS
Download (99.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentLung Inflammation1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers1
1CompletedTreatmentLipid Metabolism Disorders1
1CompletedTreatmentNeurofibromatosis 11
1CompletedTreatmentStrokes1
1TerminatedTreatmentAny Cancer / Cancer, Breast1
1, 2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2WithdrawnTreatmentSevere Persistent Asthma1
2Active Not RecruitingTreatmentJaundice / Rhabdomyolysis / Strokes1
2CompletedBasic ScienceBlood Platelets Proteome1
2CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Cholesterol / Myocardial Ischemia1
2CompletedPreventionCardiovascular Disease (CVD) / Carotid Stenosis / Cerebral Arteriosclerosis / Cerebrovascular Disorders / Heart Diseases / Vascular Diseases1
2CompletedPreventionPrecancerous Conditions / Stage 0 Melanoma / Stage I Melanoma / Stage II Melanoma1
2CompletedSupportive CareProstate Cancer1
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentFragile X Syndrome (FXS)1
2CompletedTreatmentHIV Seropositivity1
2CompletedTreatmentNeurofibromatosis Type 11
2CompletedTreatmentRett's Syndrome1
2CompletedTreatmentRheumatoid Arthritis1
2Enrolling by InvitationTreatmentFragile X Syndrome (FXS)1
2RecruitingOtherParkinson's Disease (PD)1
2RecruitingTreatmentImpaired Cognition / Impaired Synaptic Plasticity / Noonan Syndrome, Neurofibromatosis Type 11
2RecruitingTreatmentLearning Disability / Neurofibromatosis Type 1 / NF1 / Reading Disability1
2TerminatedSupportive CareCancer, Breast / Radiation Toxicity1
2TerminatedTreatmentCancer of the Ovary1
2TerminatedTreatmentCancer, Breast1
2Unknown StatusTreatmentXanthomatosis, Cerebrotendinous1
2WithdrawnTreatmentChild Syndrome / Conradi Syndrome / Smith Lemli Opitz Syndrome / Syndromic Ichthyoses1
2WithdrawnTreatmentMalignant Melanoma / Melanoma1
2, 3CompletedTreatmentAlveolar Bone Loss, Chronic Periodontitis, Lovestatin Gel, Regeneration1
2, 3CompletedTreatmentAtherosclerosis / Coronary Artery Disease1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
3CompletedPreventionHigh Cholesterol1
3CompletedTreatmentCardiovascular Disease (CVD) / Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
3CompletedTreatmentHigh Cholesterol1
3CompletedTreatmentIntermittent Claudication / Peripheral Vascular Disease (PVD)2
3RecruitingTreatmentHigh Cholesterol2
3TerminatedTreatmentHigh Cholesterol1
4CompletedTreatmentDyslipidemias / Hyperlipidemias / Mixed hypercholesterolemia1
4CompletedTreatmentFragile X Syndrome (FXS) / Genetic Diseases1
4CompletedTreatmentHealthy Volunteers2
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableHigh Cholesterol1
Not AvailableCompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers1
Not AvailableSuspendedTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
  • Andrx labs llc
  • Actavis elizabeth llc
  • Apotex inc
  • Carlsbad technology inc
  • Lupin ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Cardinal Health
  • Carlsbad Technology Inc.
  • Comprehensive Consultant Services Inc.
  • DHHS Program Support Center Supply Service Center
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Heartland Repack Services LLC
  • International Laboratories Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Lupin Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Medvantx Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Sandhills Packaging Inc.
  • Sciele Pharma Inc.
  • Shionogi Pharma Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • Yung Shin Pharmaceutical Industry Ltd.
Dosage forms
FormRouteStrength
Tablet, extended releaseOral
Tablet, extended release; tablet, multilayer, extended releaseOral
Tablet, extended releaseOral20 mg/1
Tablet, extended releaseOral40 mg/1
Tablet, extended releaseOral60 mg/1
TabletOral20 mg
TabletOral40 mg
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral40 mg/1
Prices
Unit descriptionCostUnit
Altoprev 60 mg 24 Hour tablet7.99USD tablet
Altoprev 60 mg tablet7.74USD tablet
Altoprev 20 mg 24 Hour tablet6.88USD tablet
Altoprev 20 mg tablet6.61USD tablet
Mevacor 40 mg tablet4.57USD tablet
Altoprev 40 mg tablet4.41USD tablet
Lovastatin 40 mg tablet4.36USD tablet
Altoprev 10 mg 24 Hour tablet3.07USD tablet
Mevacor 20 mg tablet2.53USD tablet
Lovastatin 20 mg tablet2.42USD tablet
Altocor 20 mg 24 Hour tablet2.36USD tablet
Apo-Lovastatin 40 mg Tablet2.11USD tablet
Co Lovastatin 40 mg Tablet2.11USD tablet
Mylan-Lovastatin 40 mg Tablet2.11USD tablet
Novo-Lovastatin 40 mg Tablet2.11USD tablet
Pms-Lovastatin 40 mg Tablet2.11USD tablet
Ran-Lovastatin 40 mg Tablet2.11USD tablet
Ratio-Lovastatin 40 mg Tablet2.11USD tablet
Sandoz Lovastatin 40 mg Tablet2.11USD tablet
Mevacor 10 mg tablet1.65USD tablet
Lovastatin 10 mg tablet1.37USD tablet
Apo-Lovastatin 20 mg Tablet1.14USD tablet
Co Lovastatin 20 mg Tablet1.14USD tablet
Mylan-Lovastatin 20 mg Tablet1.14USD tablet
Novo-Lovastatin 20 mg Tablet1.14USD tablet
Pms-Lovastatin 20 mg Tablet1.14USD tablet
Ran-Lovastatin 20 mg Tablet1.14USD tablet
Ratio-Lovastatin 20 mg Tablet1.14USD tablet
Sandoz Lovastatin 20 mg Tablet1.14USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6080428No2000-06-272017-05-27Us
US6469035No2002-10-222018-03-15Us
US6080778No2000-06-272018-03-23Us
US6485748No2002-11-262017-12-12Us
US5916595No1999-06-292017-12-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)174.5 °CNot Available
water solubility0.0004 mg/mLNot Available
logP4.26HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0243 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity113.18 m3·mol-1ChemAxon
Polarizability46.11 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9452
Blood Brain Barrier+0.9287
Caco-2 permeable-0.5484
P-glycoprotein substrateSubstrate0.7861
P-glycoprotein inhibitor IInhibitor0.7046
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterNon-inhibitor0.8299
CYP450 2C9 substrateNon-substrate0.8333
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6868
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9291
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.8475
CarcinogenicityNon-carcinogens0.9519
BiodegradationNot ready biodegradable0.8819
Rat acute toxicity2.0554 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7272
hERG inhibition (predictor II)Non-inhibitor0.7484
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-2910000000-dc8caf3905a76d1dc259
GC-MS Spectrum - EI-BGC-MSsplash10-0a4j-1910000000-8aeacab386a420581150
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0k9j-0392200000-046f8ecdd9105ec8f133
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0fg2-0590000000-79f2e6dc3b230361fea3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0092-0970000000-029f3798d63ab95ed321
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0592-0930000000-85de8f33dd78ba45de36
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fv-0910000000-7a730b8fcd91e3df5b8f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-000e-0590000000-2206c97b74e146b3218d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0092-1960000000-6b3a14df210273b89f18
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0592-1910000000-38bd634327305fe325cf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0abd-1900000000-e7dab133ffe03d435831
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0536-2900000000-12e639483c7d1a83da05
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-002f-2900000000-ed64daa9de830f1f3cb0

Taxonomy

Description
This compound 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
Fatty acid esters / Oxanes / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acid esters / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Delta valerolactone / Fatty acid ester / Delta_valerolactone / Dicarboxylic acid or derivatives / Oxane / Fatty acyl / Carboxylic acid ester / Secondary alcohol / Carboxylic acid derivative / Oxacycle
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
polyketide, fatty acid ester, delta-lactone, carbobicyclic compound, statin (naturally occurring) (CHEBI:40303)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadph binding
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...
Gene Name
HMGCR
Uniprot ID
P04035
Uniprot Name
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Molecular Weight
97475.155 Da
References
  1. Abe Y, Suzuki T, Ono C, Iwamoto K, Hosobuchi M, Yoshikawa H: Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum. Mol Genet Genomics. 2002 Jul;267(5):636-46. Epub 2002 Jun 28. [PubMed:12172803]
  2. Miyazaki A, Koieyama T, Shimada Y, Kikuchi T, Nezu H, Ito K, Kasanuki N, Koga T: Effects of pravastatin sodium on mevalonate metabolism in common marmosets. J Biochem. 2002 Sep;132(3):395-400. [PubMed:12204108]
  3. Buxbaum JD, Geoghagen NS, Friedhoff LT: Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J Alzheimers Dis. 2001 Apr;3(2):221-229. [PubMed:12214063]
  4. Baranova NA, Kreier VG, Egorov NS: [Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89]. Antibiot Khimioter. 2002;47(4):3-6. [PubMed:12369143]
  5. Farina HG, Bublik DR, Alonso DF, Gomez DE: Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis. 2002;19(6):551-9. [PubMed:12405293]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Podar K, Tai YT, Hideshima T, Vallet S, Richardson PG, Anderson KC: Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278 . [PubMed:19249983]
  8. Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S: Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. [PubMed:12082550]
Details
2. Integrin alpha-L
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other/unknown
General Function
Metal ion binding
Specific Function
Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated ...
Gene Name
ITGAL
Uniprot ID
P20701
Uniprot Name
Integrin alpha-L
Molecular Weight
128768.495 Da
References
  1. Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U: Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol. 1999 Sep 10;292(1):1-9. [PubMed:10493852]
Details
3. Histone deacetylase 2
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Other
General Function
Transcription factor binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC2
Uniprot ID
Q92769
Uniprot Name
Histone deacetylase 2
Molecular Weight
55363.855 Da
References
  1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. doi: 10.1158/0008-5472.CAN-07-5807. [PubMed:18381445]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  2. Hong SP, Yang JS, Han JY, Ha SI, Chung JW, Koh YY, Chang KS, Choi DH: Effects of lovastatin on the pharmacokinetics of diltiazem and its main metabolite, desacetyldiltiazem, in rats: possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by lovastatin. J Pharm Pharmacol. 2011 Jan;63(1):129-35. [PubMed:21189658]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. TABLETS MEVACOR® (LOVASTATIN) FDA LABEL [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- ...
Gene Name
PON3
Uniprot ID
Q15166
Uniprot Name
Serum paraoxonase/lactonase 3
Molecular Weight
39607.185 Da
References
  1. Draganov DI, Stetson PL, Watson CE, Billecke SS, La Du BN: Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem. 2000 Oct 27;275(43):33435-42. [PubMed:10931838]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Tornio A, Pasanen MK, Laitila J, Neuvonen PJ, Backman JT: Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):104-8. [PubMed:15998357]
  2. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. [PubMed:15601807]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supporting this enzyme action are limited to findings of an in vitro study.
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Transon C, Leemann T, Dayer P: In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15. [PubMed:8737761]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Transon C, Leemann T, Dayer P: In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15. [PubMed:8737761]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, Baillie TA: Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos. 2002 May;30(5):505-12. [PubMed:11950779]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Wang E, Casciano CN, Clement RP, Johnson WW: HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res. 2001 Jun;18(6):800-6. [PubMed:11474784]
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514]
  3. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. [PubMed:10213372]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. [PubMed:10421612]
  2. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. [PubMed:10601278]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. [PubMed:10601278]
  2. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. [PubMed:15716364]
  3. Kunze A, Huwyler J, Camenisch G, Poller B: Prediction of organic anion-transporting polypeptide 1B1- and 1B3-mediated hepatic uptake of statins based on transporter protein expression and activity data. Drug Metab Dispos. 2014 Sep;42(9):1514-21. doi: 10.1124/dmd.114.058412. Epub 2014 Jul 2. [PubMed:24989890]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Ellis LC, Hawksworth GM, Weaver RJ: ATP-dependent transport of statins by human and rat MRP2/Mrp2. Toxicol Appl Pharmacol. 2013 Jun 1;269(2):187-94. doi: 10.1016/j.taap.2013.03.019. Epub 2013 Apr 2. [PubMed:23562342]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:32