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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 of LOVASTATIN

SMILES

CC[C@H](C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@@H]12

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
Defined Stereocenters 8 / 8
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

PubMed

PubMed

TitleDatePubMed
Discovery, biochemistry and biology of lovastatin.
1988 Nov 11
Coronary angiographic changes with lovastatin therapy. The Monitored Atherosclerosis Regression Study (MARS).
1993 Nov 15
Phase II study of high-dose lovastatin in patients with advanced gastric adenocarcinoma.
2001
The cyclin dependent kinase inhibitor p27 and its prognostic role in breast cancer.
2001
An analysis of nine proprietary Chinese red yeast rice dietary supplements: implications of variability in chemical profile and contents.
2001 Apr
The effects of the statins lovastatin and cerivastatin on signalling by the prostanoid IP-receptor.
2001 Apr
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.
2001 Apr
A new simvastatin (mevinolin)-resistance marker from Haloarcula hispanica and a new Haloferax volcanii strain cured of plasmid pHV2.
2001 Apr
Antiviral activity of lovastatin against respiratory syncytial virus in vivo and in vitro.
2001 Apr
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.
2001 Apr
Rho GTPases are involved in the regulation of NF-kappaB by genotoxic stress.
2001 Apr 1
Statins are magic when you gotta have heart.
2001 Apr 16
Assessing the results: phase 1 hyperlipidemia outcomes in 27 health plans.
2001 Apr 16
Differential effects of lovastatin treatment on brain cholesterol levels in normal and apoE-deficient mice.
2001 Apr 17
Analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors using liquid chromatography-electrospray mass spectrometry.
2001 Apr 25
Deterioration of the protein kinase C-K(ATP) channel pathway in regulation of coronary flow in hypercholesterolaemic rabbits.
2001 Apr 27
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
Interaction of cytosine arabinoside and lovastatin in human leukemia cells.
2001 Aug
Low-dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low-density lipoprotein cholesterol in patients with primary hypercholesterolemia.
2001 Jun
Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection.
2001 Jun
Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site.
2001 Jun
Use of statins and the subsequent development of deep vein thrombosis.
2001 Jun 11
Compactin enhances osteogenesis in murine embryonic stem cells.
2001 Jun 8
Recent advances in the biosynthetic studies of lovastatin.
2001 Mar
[Statins do not prevent restenosis after coronary angioplasty: where to go from here?].
2001 Mar
[AFCAPS/TexCAPS [The Air Force/Texas Coronary Atherosclerosis Prevention Study]].
2001 Mar
Lovastatin blocks basic fibroblast growth factor-induced mitogen-activated protein kinase signaling in coronary smooth muscle cells via phosphatase inhibition.
2001 Mar
[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].
2001 Mar
Is a statin a statin?
2001 Mar
Lovastatin and phenylacetate induce apoptosis, but not differentiation, in human malignant glioma cells.
2001 Mar
HMG-CoA reductase inhibitors and P-glycoprotein modulation.
2001 Mar
Inhibition of human tumor cell growth in vivo by an orally bioavailable inhibitor of human farnesyltransferase, BIM-46228.
2001 Mar 1
Liver regeneration after hepatectomy.
2001 Mar-Apr
New OTC drugs and devices 2000: a selective review.
2001 Mar-Apr
The National Service Framework on coronary heart disease: is it sufficiently evidence-based?
2001 May
Statin induced myopathy does not show up in MIBI scintigraphy.
2001 May
Revised indications for statin therapies.
2001 May
What do the statin trials tell us?
2001 May
Statins--similarities and differences.
2001 May
Should all patients with cardiovascular disease receive statin therapy?
2001 May
Long-term administration of the HMG-CoA reductase inhibitor lovastatin in two patients with cholesteryl ester storage disease.
2001 May
Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate.
2001 May
The combined effects of novel tocotrienols and lovastatin on lipid metabolism in chickens.
2001 May
Can modulation of endothelial nitric oxide synthase explain the vasculoprotective actions of statins?
2001 May
Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.
2001 May
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TEXCAPS): additional perspectives on tolerability of long-term treatment with lovastatin.
2001 May 1
RhoA is activated during respiratory syncytial virus infection.
2001 May 10
Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.
2001 May 18
Lovastatin controls signal transduction in vascular smooth muscle cells by modulating phosphorylation levels of mevalonate-independent pathways.
2001 May-Jun
Cost effectiveness of HMG-CoA reductase inhibition in Canada.
2001 Spring
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 Tue Oct 22 00:19:35 UTC 2019
Edited
by admin
on Tue Oct 22 00:19:35 UTC 2019
Record UNII
9LHU78OQFD
Record Status Validated (UNII)
Record Version
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Name Type Language
LOVASTATIN
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
SIMVASTATIN IMPURITY, LOVASTATIN- [USP]
Common Name English
LOVASTATIN [USP-RS]
Common Name English
LOVASTATIN [WHO-DD]
Common Name English
LOVASTATIN [EP]
Common Name English
MEVLOR
Brand Name English
LOVASTATIN COMPONENT OF ADVICOR
Common Name English
SIVLOR
Brand Name English
SIMVASTATIN SPECIFIED IMPURITY E [EP]
Common Name English
LOVASTATIN [INN]
Common Name English
ALTOPREV
Brand Name English
MEVINOLIN
Common Name English
L-154803
Code English
LOVASTATIN [ORANGE BOOK]
Common Name English
MONACOLIN K
Common Name English
MK-803
Code English
LOVASTATIN [HSDB]
Common Name English
LOVASTATIN [USP]
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
MEVACOR
Brand Name English
6.ALPHA.-METHYLCOMPACTIN
Common Name English
Classification Tree Code System Code
WHO-ATC C10AA02
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
LIVERTOX 574
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
WHO-ATC C10BA01
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
NCI_THESAURUS C54679
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
WHO-VATC QC10BA01
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
WHO-VATC QC10AA02
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
NDF-RT N0000000121
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
NCI_THESAURUS C1655
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
NDF-RT N0000175589
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
Code System Code Type Description
HSDB
75330-75-5
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
LactMed
75330-75-5
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
INN
6074
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
MERCK INDEX
M6914
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY Merck Index
ChEMBL
CHEMBL503
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
EPA CompTox
75330-75-5
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
MESH
D008148
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
DRUG BANK
DB00227
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
RXCUI
6472
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY RxNorm
NCI_THESAURUS
C620
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
PUBCHEM
53232
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
EVMPD
SUB08604MIG
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
CAS
75330-75-5
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
IUPHAR
2739
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
WIKIPEDIA
LOVASTATIN
Created by admin on Tue Oct 22 00:19:35 UTC 2019 , Edited by admin on Tue Oct 22 00:19:35 UTC 2019
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
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METABOLITE -> PARENT
CYP3A
PLASMA
METABOLITE ACTIVE -> PRODRUG
METABOLITE -> PARENT
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IN-VITRO
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PARENT -> IMPURITY
sum of impurities E and F: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (1.0 per cent)
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
MAXIMUM TOLERATED DOSE TOXICITY
ORAL BIOAVAILABILITY PHARMACOKINETIC