LOVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H36O5
Molecular Weight	404.5396
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]3C[C@@H](O)CC(=O)O3)OC(=O)[C@@H](C)CC

InChI

InChIKey=PCZOHLXUXFIOCF-BXMDZJJMSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdf
Curator's Comment: description was created based on several sources, including https://clinicaltrials.gov/show/NCT00580970 | http://medical-dictionary.thefreedictionary.com/lovastatin

Lovastatin acid is an active metabolite of hypolipidemic drug Lovastatin. Lovastatin acid inhibits HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol. Lovastatin has been shown to reduce both normal and elevated low-density lipoprotein cholesterol (LDL-C). Lovastatin in approved for prevention of cardiovascular events and hypercholesterolemia. Off-label use of lovastatin includes treatmetn of diabetic dyslipidemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia, or nephrotic hyperlipidemia. Lovastatin was tested in clinical trials agains radioation injury during therapy of prostate cancer.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3055919	Inhibitor 8297		0.64 nM [IC50]
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12405293	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Coronary heart disease 41 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdf	Preventing	Approved 8429	ALTOPREV Approved Use 1.1 Prevention of Coronary Heart Disease In patients without symptomatic coronary heart disease (CHD), but at high risk, Altoprev® is indicated to reduce the risk of: Myocardial infarction; Unstable angina; Coronary revascularization procedures; Coronary Heart Disease. Altoprev is indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower Total-C and LDL-C to target levels. Hyperlipidemia Altoprev is indicated as an adjunct to diet for the reduction of elevated Total-C, LDL-C, Apo B, and TG, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb). Launch Date 2002
Hyperlipidemia 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdf	Palliative	Approved 8429	ALTOPREV Approved Use 1.1 Prevention of Coronary Heart Disease In patients without symptomatic coronary heart disease (CHD), but at high risk, Altoprev® is indicated to reduce the risk of: Myocardial infarction; Unstable angina; Coronary revascularization procedures; Coronary Heart Disease. Altoprev is indicated to slow the progression of coronary atherosclerosis in patients with coronary heart disease as part of a treatment strategy to lower Total-C and LDL-C to target levels. Hyperlipidemia Altoprev is indicated as an adjunct to diet for the reduction of elevated Total-C, LDL-C, Apo B, and TG, and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and non-familial) and mixed dyslipidemia (Fredrickson types IIa and IIb). Launch Date 2002
Atherosclerotic cardiovascular disease 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdf	Preventing	Approved 8429	MEVACOR Approved Use After oral ingestion, lovastatin, which is an inactive lactone, is hydrolyzed to the lovastatin acid. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol. Lovastatin has been shown to reduce both normal and elevated low-density lipoprotein cholesterol (LDL-C). Launch Date 1987
Hypercholesterolemia 47 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdf	Primary	Approved 8429	MEVACOR Approved Use Therapy with lipid-altering agents should be a component of multiple risk factor intervention in those individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. MEVACOR is indicated as an adjunct to diet for the reduction of elevated total-C and LDL-C levels in patients with primary hypercholesterolemia (Types IIa and IIb***), when the response to diet restricted in saturated fat and cholesterol and to other nonpharmacological measures alone has been inadequate. Launch Date 1987
Prostate cancer 178 Sources: https://clinicaltrials.gov/show/NCT00580970	Secondary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
17.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9585793	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
11.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021316s028lbl.pdf	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
76.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9585793	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
83 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021316s028lbl.pdf	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9585793	80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021316s028lbl.pdf	40 mg 1 times / day steady-state, oral dose: 40 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		LOVASTATIN ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
80 mg 1 times / day multiple, oral (max) Recommended Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8481075 Page: p.1082, 1083	unhealthy, 50 n = 745 Health Status: unhealthy Condition: Hypercholesterolemia Age Group: 50 Sex: M+F Population Size: 745 Sources: https://pubmed.ncbi.nlm.nih.gov/8481075 Page: p.1082, 1083	Disc. AE: Aspartate aminotransferase increased, Alanine aminotransferase increased... AEs leading to discontinuation/dose reduction: Aspartate aminotransferase increased (grade 2-4, 1.3%) Alanine aminotransferase increased (grade 2-4, 1.3%) Gastrointestinal disturbance (0.4%) Rash (0.27%) Myalgia (0.13%) Myopathy (0.27%) Arthralgia (0.13%) Insomnia (0.13%) Weight gain (0.13%) Sources: https://pubmed.ncbi.nlm.nih.gov/8481075 Page: p.1082, 1083
10 mg/kg 4 times / day multiple, oral (total daily dose) Highest studied dose Dose: 10 mg/kg, 4 times / day Route: oral Route: multiple Dose: 10 mg/kg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527	unhealthy, 56 n = 6 Health Status: unhealthy Condition: Squamous cell carcinoma of the head and neck \|Squamous cell carcinoma of the cervix Age Group: 56 Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527	DLT: Creatine phosphokinase increased, Aspartate aminotransferase increased... Dose limiting toxicities: Creatine phosphokinase increased (grade 4, 33.3%) Aspartate aminotransferase increased (grade 2-3, 33.3%) Alanine aminotransferase increased (grade 2-3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527
7.5 mg/kg 4 times / day multiple, oral (total daily dose) MTD Dose: 7.5 mg/kg, 4 times / day Route: oral Route: multiple Dose: 7.5 mg/kg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527	unhealthy, 56 n = 7 Health Status: unhealthy Condition: Squamous cell carcinoma of the head and neck \|Squamous cell carcinoma of the cervix Age Group: 56 Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527	DLT: Creatine phosphokinase increased, Aspartate aminotransferase increased... Dose limiting toxicities: Creatine phosphokinase increased (grade 4, 28.6%) Aspartate aminotransferase increased (grade 3, 14.3%) Alanine aminotransferase increased (grade 3, 14.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/15737556 Page: p.527

AEs

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-032461	http://www.3bsc.com/index/pro_info.php?id=53725
ABI Chem	AC1L21T5
ABI Chem	AC1Q2C7S
AHH Chemical co.,ltd	MT-53300	http://www.ahhchemical.com/product/MT-53300.html
AK Scientific	O686
BOC Sciences	237073-64-2
BOC Sciences	75225-50-2
Cayman Chemical	10010339
ChemShuttle	159863	http://www.chemshuttle.com/catalogsearch/result/?q=75225-50-2&cat=
Chemieliva Pharmaceutical Co., Ltd	PBCM1407363
Compound Cloud	64727
MolPort	MolPort-003-848-427
Molcan	lovastatin-acid
NovoSeek	64727
OChem	21141	http://www.ocheminc.com/index.php?act=psearch&pid=225L502
Tetrahedron	TS82164
Toronto Research Chemicals	B278835
Toronto Research Chemicals	L472250
Toronto Research Chemicals	M261505
ZINC	ZINC000004134473	http://zinc15.docking.org/substances/ZINC000004134473
eMolecules	222583559
eMolecules	29935032
eMolecules	313069140
eMolecules	48853411
eNovation Chemicals	D701037	https://www.enovationchem.com/ProductDetails.asp?ProductID=D701037

PubMed

Title	Date	PubMed
Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma.	2001	11291836
The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer.	2001	11250752
An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents.	2001 Apr	11327519
The effects of the statins lovastatin and cerivastatin on signalling by the prostanoid IP-receptor.	2001 Apr	11309234
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.	2001 Apr	11283400
A new simvastatin (mevinolin)-resistance marker from Haloarcula hispanica and a new Haloferax volcanii strain cured of plasmid pHV2.	2001 Apr	11283291
Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro.	2001 Apr	11257039
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.	2001 Apr	11254918
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts.	2001 Apr	11241350
Rho GTPases are involved in the regulation of NF-kappaB by genotoxic stress.	2001 Apr 1	11262181
Statins are magic when you gotta have heart.	2001 Apr 16	11330169
Assessing the results: phase 1 hyperlipidemia outcomes in 27 health plans.	2001 Apr 16	11311193
Differential effects of lovastatin treatment on brain cholesterol levels in normal and apoE-deficient mice.	2001 Apr 17	11303752
Analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors using liquid chromatography-electrospray mass spectrometry.	2001 Apr 25	11339276
Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits.	2001 Apr 27	11343693
The widening role of statins: RAS signal transduction and drug-induced cytotoxicity in human leukemia: a commentary to 'interaction of cytosine arabinoside and lovastatin in human leukemia cells'.	2001 Aug	11397470
Interaction of cytosine arabinoside and lovastatin in human leukemia cells.	2001 Aug	11397469
Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia.	2001 Jun	11403509
Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.	2001 Jun	11389707
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.	2001 Jun	11385505
Use of statins and the subsequent development of deep vein thrombosis.	2001 Jun 11	11386889
Compactin enhances osteogenesis in murine embryonic stem cells.	2001 Jun 8	11394905
Recent advances in the biosynthetic studies of lovastatin.	2001 Mar	11378962
[Statins do not prevent restenosis after coronary angioplasty: where to go from here?].	2001 Mar	11349614
[AFCAPS/TexCAPS [The Air Force/Texas Coronary Atherosclerosis Prevention Study]].	2001 Mar	11347102
Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition.	2001 Mar	11322384
[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].	2001 Mar	11321957
Is a statin a statin?	2001 Mar	11321864
Lovastatin and phenylacetate induce apoptosis, but not differentiation, in human malignant glioma cells.	2001 Mar	11307620
HMG-CoA reductase inhibitors and P-glycoprotein modulation.	2001 Mar	11250868
Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of human farnesyltransferase, BIM-46228.	2001 Mar 1	11267986
High apolipoprotein B with low high-density lipoprotein cholesterol and normal plasma triglycerides and cholesterol.	2001 Mar 15	11249908
Liver regeneration after hepatectomy.	2001 Mar-Apr	11379353
New OTC drugs and devices 2000: a selective review.	2001 Mar-Apr	11297337
The National Service Framework on coronary heart disease: is it sufficiently evidence-based?	2001 May	11392491
Statin induced myopathy does not show up in MIBI scintigraphy.	2001 May	11388581
Revised indications for statin therapies.	2001 May	11386390
What do the statin trials tell us?	2001 May	11383375
Statins--similarities and differences.	2001 May	11383374
Should all patients with cardiovascular disease receive statin therapy?	2001 May	11383372
Long-term administration of the HMG-CoA reductase inhibitor lovastatin in two patients with cholesteryl ester storage disease.	2001 May	11380065
Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate.	2001 May	11372002
The combined effects of novel tocotrienols and lovastatin on lipid metabolism in chickens.	2001 May	11368995
Can modulation of endothelial nitric oxide synthase explain the vasculoprotective actions of statins?	2001 May	11325618
Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.	2001 May	11318945
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin.	2001 May 1	11348605
RhoA is activated during respiratory syncytial virus infection.	2001 May 10	11336544
Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.	2001 May 18	11278785
Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways.	2001 May-Jun	11403422
Cost effectiveness of HMG-CoA reductase inhibition in Canada.	2001 Spring	11283756

Patents

Sample Use Guides

In Vivo Use Guide

Hyperlipidemia and Mixed Dyslipidemia: (Fredrickson Types IIa and IIb). The recommended dosing range is 20-60 mg/day, in single doses taken in the evening at bedtime.

Route of Administration: Oral

In Vitro Use Guide

Flow cytometry revealed significant increases in three of four lung cancer cell lines in apoptosis and necrosis after lovastatin treatment at 10 uM for 72 h. Lovastatin adversely affected lung cancer cell survival with increases in cell-cycle check-point inhibitors p21WAF and/or p27KIP and a decrease in cyclin D1. All four lung cancer cell lines had a decrease in glutathione after lovastatin treatment consistent with reduced protection against reactive oxidant species. Three of four lung cancer cell lines had increased cytochrome c release with reduced pro-caspase-3 and increases in activated caspase-3. Lovastatin induces apoptosis and necrosis in lung cancer cell lines by causing alterations in the cell cycle, reducing glutathione, and activating p53, Bax protein, and caspases while increasing cytochrome c in apoptosis pathways.

Name

Type

Language

LOVASTATIN

Official Name

English

(S)-2-Methylbutyric 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-one

Common Name

English

LOVASTATIN [USP-RS]

Common Name

English

SIMVASTATIN IMPURITY, LOVASTATIN- [USP IMPURITY]

Common Name

English

MEVLOR

Brand Name

English

LOVASTATIN COMPONENT OF ADVICOR

Common Name

English

SIVLOR

Brand Name

English

LOVASTATIN [EP MONOGRAPH]

Common Name

English

lovastatin [INN]

Common Name

English

ALTOPREV

Brand Name

English

LOVASTATIN [USP MONOGRAPH]

Common Name

English

MEVINOLIN

Common Name

English

L-154803

Code

English

LOVASTATIN [ORANGE BOOK]

Common Name

English

MONACOLIN K

Common Name

English

SIMVASTATIN IMPURITY E [EP IMPURITY]

Common Name

English

MK-803

Code

English

LOVASTATIN [HSDB]

Common Name

English

Lovastatin [WHO-DD]

Common Name

English

LOVASTATIN [MI]

Common Name

English

LOVASTATIN [MART.]

Common Name

English

C10AA02

Code

English

LOVASTATIN [USAN]

Common Name

English

BUTANOIC ACID, 2-METHYL-, 1,2,3,7,8,8A-HEXAHYDRO-3,7-DIMETHYL-8-(2-(TETRAHYDRO-4-HYDROXY-6-OXO-2H-PYRAN-2-YL)ETHYL)-1-NAPHTHALENYL ESTER, (1S-(1.ALPHA.(R*),3.ALPHA.,7.BETA.,8.BETA.(2S*,4S*),8.ALPHA..BETA.))-

Common Name

English

ADVICOR COMPONENT LOVASTATIN

Common Name

English

(2S)-2-METHYLBUTANOIC ACID (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 ESTER

Common Name

English

MEVINACOR

Brand Name

English

LOVASTATIN [VANDF]

Common Name

English

NSC-758662

Code

English

MEVACOR

Brand Name

English

6.ALPHA.-METHYLCOMPACTIN

Common Name

English

Classification Tree Code System Code

WHO-ATC

C10AA02