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

Molecular Formula	C24H36O5
Molecular Weight	404.5396
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20467214

Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. Alfred Alberts and his team at Merck discovered it 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. The primary uses of lovastatin is for the treatment of dyslipidemia and the prevention of cardiovascular disease. Lovastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a strong inhibitor of HMG-CoA reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol. Lovastatin, as well as some of its metabolites, are pharmacologically active in humans. The liver is the primary site of action and the principal site of cholesterol synthesis and LDL clearance. The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL-C and low high-density lipoprotein cholesterol (HDL-C) levels are both associated with coronary heart disease. However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (Total-C) and LDL-C levels in the lower end of this range. Lovastatin immediate-release tablets have been shown to reduce elevated LDL-C concentrations. LDL is formed from very low-density lipoprotein (VLDL) and is catabolized predominantly by the high-affinity LDL receptor. The mechanism of the LDL-lowering effect of lovastatin immediate-release may involve both reduction of VLDL-C concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-C.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 46 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3055919	Inhibitor 8228		0.64 nM [IC50]
HMG-CoA reductase 46 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12405293	Inhibitor 8228

Conditions

Condition	Modality	Highest Phase	Product
Coronary heart disease 23 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdf	Preventing	Approved 8360	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 1.01200318E12
Hyperlipidemia 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021316s031lbl.pdf	Palliative	Approved 8360	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 1.01200318E12
Atherosclerotic cardiovascular disease 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdf	Preventing	Approved 8360	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 5.5728E11
Hypercholesterolemia 47 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/019643s085lbl.pdf	Primary	Approved 8360	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 5.5728E11
Prostate cancer 175 Sources: https://clinicaltrials.gov/show/NCT00580970	Secondary	Phase II 1144	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
Discovery, biochemistry and biology of lovastatin.	1988 Nov 11	3055919
Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).	1993 Nov 15	8214993
Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells.	1999 Aug	10473109
Effect of lipid-lowering strategies on tubular cell biology.	1999 Jul	10412747
Lovastatin-induced apoptosis of human medulloblastoma cell lines in vitro.	1999 Mar	10360474
Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac.	1999 Oct	10500066
Lovastatin inhibits G1/S transition of normal human B-lymphocytes independent of apoptosis.	1999 Oct 10	10502407
Differences in the effects of HMG-CoA reductase inhibitors on proliferation and viability of smooth muscle cells in culture.	2000 Jun	10856525
Increased lipid peroxidation in a patient with CK-elevation and muscle pain during statin therapy.	2000 Nov	11058722
Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation.	2000 Oct 27	10931838
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
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.	2001 Apr	11283400
Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro.	2001 Apr	11257039
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
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
[Endocrine disease in adrenoleukodystrophy].	2001 Feb	11240421
[Practical questions for the expert].	2001 Feb	11240418
[Statins: a major therapeutic breakthrough].	2001 Feb	11240410
Do HMG-CoA reductase inhibitors affect fibrinogen?	2001 Feb	11215845
Mechanisms for cholesterol homeostasis in rat jejunal mucosa: effects of cholesterol, sitosterol, and lovastatin.	2001 Feb	11181748
Bimonthly update. Therapy and clinical trials.	2001 Feb	11176209
Nitrogen-bisphosphonates block retinoblastoma phosphorylation and cell growth by inhibiting the cholesterol biosynthetic pathway in a keratinocyte model for esophageal irritation.	2001 Feb	11160853
Butyrate-induced differentiation of Caco-2 cells occurs independently from p27.	2001 Feb 23	11181044
Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin.	2001 Jan	11197581
Molecular effects of HMG-CoA reductase inhibitors on smooth muscle cell proliferation.	2001 Jan	11153768
Reduction of LDL cholesterol in patients with primary hypercholesterolemia by SCH 48461: results of a multicenter dose-ranging study.	2001 Jan	11144997
The benefits of niacin in atherosclerosis.	2001 Jan	11123852
Statins in children: what do we know and what do we need to do?	2001 Jan	11123845
New statins and new doses of older statins.	2001 Jan	11123843
Statin trials in progress: unanswered questions.	2001 Jan	11123842
Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia.	2001 Jun	11403509
[Statins do not prevent restenosis after coronary angioplasty: where to go from here?].	2001 Mar	11349614
[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].	2001 Mar	11321957
Is a statin a statin?	2001 Mar	11321864
A comparison of the effects of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase inhibitors on the CYP3A4-dependent oxidation of mexazolam in vitro.	2001 Mar	11181496
3-Hydroxy-3-methylglutaryl coenzyme A synthase-1 of Blattella germanica has structural and functional features of an active retrogene.	2001 Mar 15	11222952
Liver regeneration after hepatectomy.	2001 Mar-Apr	11379353
New OTC drugs and devices 2000: a selective review.	2001 Mar-Apr	11297337
Statin induced myopathy does not show up in MIBI scintigraphy.	2001 May	11388581
Revised indications for statin therapies.	2001 May	11386390
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
Can modulation of endothelial nitric oxide synthase explain the vasculoprotective actions of statins?	2001 May	11325618
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
Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways.	2001 May-Jun	11403422

Patents

Sample Use Guides

In Vivo Use Guide

Lovastatin is administered orally with the evening meal. Maximal daily dose for adults is 80 mg, maximal dose for children is 40 mg.

Route of Administration: Oral

In Vitro Use Guide

HMG-CoA reductase from rat liver microsomes was solubilizes and purified through the second ammonium sulfate precipitation. Prior to use, the enzyme was activated at 37C for 30 min. The reaction mix contained, in 100 uL: 0.14 M potassium phosphate buffer, pH 6.8; 0.18 M KCI; 3.5 mM EDTA, pH 7.0; 10 mM dithiothreitol; bovine serum albumin at 0.1 mg/ml; 0.02 uCi of [14C]HMG-CoA and 0.3 pg of partially purified enzyme (specific activity 100-150 nmol min-1 mg-1) with or without inhibitor. After 5-min incubation at 37C, the reaction was initiated with 0.2 mM NADPH. The reaction was terminated with 20 Al of 5 M HCL. After an additional incubation for 15 min at 370C to allow for complete lactonization of the product, mevalonate, the mixture was passed over a 0.5 X 5 cm column containing 100-200 mesh Bio-Rex, chloride form (Bio-Rad), which was equilibrated with distilled water. With this resin the unreacted [14C]HMG-CoA was adsorbed and the product, [14C]mevalonolactone, was eluted with 3 ml of distilled water directly into scintillation vials. After the addition of 10 ml of Aquasol II, radioactivities of the samples were measured in a scintillation counter. Lovastatin acid inhibited HMG-CoA reductase with Ki of 0.64 nM.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:37:10 UTC 2023` Edited by `admin` on `Wed Jul 05 22:37:10 UTC 2023`
Record UNII	9LHU78OQFD
Record Status	`Validated (UNII)`
Record Version

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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