MEVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H34O5
Molecular Weight	390.5131
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12[C@H](CCC=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=AJLFOPYRIVGYMJ-INTXDZFKSA-N

InChI=1S/C23H34O5/c1-4-14(2)23(26)28-20-7-5-6-16-9-8-15(3)19(22(16)20)11-10-18-12-17(24)13-21(25)27-18/h6,8-9,14-15,17-20,22,24H,4-5,7,10-13H2,1-3H3/t14-,15-,17+,18+,19-,20-,22-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15531275 | https://www.ncbi.nlm.nih.gov/pubmed/28147319https://www.ncbi.nlm.nih.gov/pubmed/8121646
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27581384 | https://www.ncbi.nlm.nih.gov/pubmed/3981532

Mevinic acid is reversible competitive inhibitors of HMG-CoA reductase (Ki in the range of 0.2-1 nM). Mevinic acid is a precursor of a Mevastatin (mevinic acid lactone) -- a hypolipidemic agent that belongs to the statins class. Mevastatin inactive until metabolized in the liver to the open-ring hydroxy acid (Mevinic acid). Mevastatin might be considered the first statin drug; clinical trials on mevastatin were performed in the late 1970s in Japan, but it was never marketed.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
3-hydroxy-3-methylglutaryl-coenzyme A reductase 9 Target ID: P04035 Gene ID: 3156.0 Gene Symbol: HMGCR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/16386050	Inhibitor 8297
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8121646	Inhibitor 8297		1.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Familial hypercholesterolemia 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15531275	Primary	Not Provided 504	Unknown Approved Use Unknown
Triple-negative breast cancer 12 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28147319	Primary	Basic research	Unknown Approved Use Unknown
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18199328	Palliative	Basic research	Unknown Approved Use Unknown
Unknown 2578

PubMed

Title	Date	PubMed
Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity.	1976 Dec 31	16386050
Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells.	2000 May 19	10814523
Simvastatin modulates cytokine-mediated endothelial cell adhesion molecule induction: involvement of an inhibitory G protein.	2000 Sep 1	10946302
Cell cycle-related changes in regulatory volume decrease and volume-sensitive chloride conductance in mouse fibroblasts.	2001 Apr	11241350
Modulation of COX-2 expression by statins in human aortic smooth muscle cells. Involvement of geranylgeranylated proteins.	2001 Dec 14	11591701
HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2.	2001 Jul	11408350
Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.	2001 May	11318945
Lipophilic statins can be osteogenic by promoting osteoblastic calcification in a Cbfa1- and BMP-2-independent manner.	2001 Sep	11771853
The discovery and development of atorvastatin, a potent novel hypolipidemic agent.	2002	12516521
Mevastatin, an inhibitor of HMG-CoA reductase, induces apoptosis, differentiation and Rap1 expression in HL-60 cells.	2002	12403272
The role of statins as potential targets for bone formation.	2002	12106493
Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs.	2002 Apr	11956737
Double-edged role of statins in angiogenesis signaling.	2002 Apr 5	11934843
Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin.	2002 Aug 1	12147302
Mevastatin induces degeneration and decreases viability of cAMP-induced differentiated neuroblastoma cells in culture by inhibiting proteasome activity, and mevalonic acid lactone prevents these effects.	2002 Jun 1	12111853
Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway.	2002 May 1	11980672
A cell-based reporter gene assay for determining induction of CYP3A4 in a high-volume system.	2002 Oct	12235278
Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient.	2002 Oct 27	12438974
Statins as immunomodulators: comparison with interferon-beta 1b in MS.	2002 Oct 8	12370451
Inhibitor studies of isopentenyl pyrophosphate biosynthesis in suspension cultures of the yew Taxus chinensis var. mairei.	2003 Feb	12578550
Statins stimulate arachidonic acid release and prostaglandin I2 production in rat liver cells.	2003 Mar 12	12689340
Cholesterol-modulating agents kill acute myeloid leukemia cells and sensitize them to therapeutics by blocking adaptive cholesterol responses.	2003 May 1	12506040
Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase lower fecundity in the German cockroach: correlation between the effects on fecundity in vivo with the inhibition of enzymatic activity in embryo cells.	2003 Oct	14561068
Increased expression of plasminogen activator inhibitor-1 by mediators of the acute phase response: a potential progenitor of vasculopathy in hypertensives.	2003 Sep	14620928
Chronic mevastatin modulates receptor-dependent vascular contraction in eNOS-deficient mice.	2004 Aug	15130878
Statins prevent bisphosphonate-induced gamma,delta-T-cell proliferation and activation in vitro.	2004 Feb	14969398
Differential effects of lipid-lowering agents on human cholinesterases.	2004 Jan	14675561
Statins potentiate caspase-3 activity in immortalized murine neurons.	2004 Jan 23	14729230
Depletion of membrane cholesterol causes ligand-independent activation of Fas and apoptosis.	2004 Jul 16	15207716
[In vitro effects of mevastatin on the proliferation and apoptosis in human multiple myeloma cell line U266].	2004 Jun	15228663
Mevastatin-induced apoptosis and growth suppression in U266 myeloma cells.	2004 May-Jun	15274361
Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis.	2004 Oct	15474095
Disruption of lipid rafts causes apoptotic cell death in HaCaT keratinocytes.	2005 Apr	15810884
Statins potentiate the IFN-gamma-induced upregulation of group IIA phospholipase A2 in human aortic smooth muscle cells and HepG2 hepatoma cells.	2005 Apr 15	15863363
Kruppel-like factor 2 as a novel mediator of statin effects in endothelial cells.	2005 Aug 2	16043642
Three-dimensional quantitative structure (3-D QSAR) activity relationship studies on imidazolyl and N-pyrrolyl heptenoates as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitors by comparative molecular similarity indices analysis (CoMSIA).	2005 Feb 15	15686906
Mevastatin induces apoptosis in HL60 cells dependently on decrease in phosphorylated ERK.	2005 Jan	15786722
Inhibitory effects of mevastatin and a geranylgeranyl transferase I inhibitor (GGTI-2166) on mononuclear osteoclast formation induced by receptor activator of NF kappa B ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha).	2005 Jan 1	15588717
Regulation of HMG-CoA reductase in MCF-7 cells by genistein, EPA, and DHA, alone and in combination with mevastatin.	2005 Jun 28	15914273
Cholesterol modulation of the expression of mitochondrial aconitase in human prostatic carcinoma cells.	2005 Jun 30	16201454
HMG CoA reductase inhibitors (statins) to treat Epstein-Barr virus-driven lymphoma.	2005 May 9	15856040
Cholesterol biosynthesis and the pro-apoptotic effects of the p75 nerve growth factor receptor in PC12 pheochromocytoma cells.	2005 Oct 3	15967538
Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil.	2005 Sep 9	16081098
Alkylamines cause Vgamma9Vdelta2 T-cell activation and proliferation by inhibiting the mevalonate pathway.	2006 Jan 15	16179378
Statins inhibit growth of human endometrial stromal cells independently of cholesterol availability.	2006 Jul	16571871
HMG-CoA reductase inhibitors induce apoptosis in pericytes.	2006 Mar	16427097

Patents

Sample Use Guides

In Vivo Use Guide

from 30 to 60 mg per day for 24 weeks

Route of Administration: Oral

In Vitro Use Guide

Mevastatin induced a profound concentration-dependent inhibition of DNA synthesis. At the highest concentration (30 microM), mevastatin inhibited DNA synthesis by 92%. Similarly, in the MTT proliferation assay, mevastatin induced a concentration-dependent decrease in cell number. Mevastatin decreased production of P (by up to 49%) and T (by up to 52%); these effects remained significant when the effect on cell culture protein content was accounted for.

Name

Type

Language

MEVASTATIN

Official Name

English

L637312

Code

English

ML236B lactone

Code

English

NSC-281245

Code

English

(1S,7S,8S,8AR)-1,2,3,7,8,8A-HEXAHYDRO-7-METHYL-8-(2-((2R,4R)-TETRAHYDRO-4-HYDROXY-6-OXO-2H-PYRAN-2-YL)ETHYL)-1-NAPHTHYL (S)-2-METHYLBUTYRATE

Common Name

English

NSC-759322

Code

English

NSC281245

Code

English

mevastatin [INN]

Common Name

English

L-637312

Code

English

MEVASTATIN [USP-RS]

Common Name

English

CS-500

Code

English

ML-236B lactone

Code

English

(+)-Compactin

Common Name

English

CS500

Code

English

MEVASTATIN [MART.]

Common Name

English

LOVASTATIN IMPURITY A [EP IMPURITY]

Common Name

English

MEVASTATIN [MI]

Common Name

English

COMPACTIN

Common Name

English

MEVASTATIN [JAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1655