MEGLUTOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C6H10O5
Molecular Weight	162.1406
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)(CC(O)=O)CC(O)=O

InChI

InChIKey=NPOAOTPXWNWTSH-UHFFFAOYSA-N

InChI=1S/C6H10O5/c1-6(11,2-4(7)8)3-5(9)10/h11H,2-3H2,1H3,(H,7,8)(H,9,10)

HIDE SMILES / InChI

Molecular Formula	C6H10O5
Molecular Weight	162.1406
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/mesh/68015093 | https://www.ncbi.nlm.nih.gov/pubmed/6180274

Meglutol (3-Hydroxy-3-methylglutaric acid, HMGA) is an antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids, and inhibits the activity of hydroxymethylglutarryl CoA reductases, which is the rate-limiting enzyme in the biosynthesis of cholesterol. 3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. In hamster model HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15686898	Inhibitor 8297		4.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypercholesterolemia 47 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6180274	Primary		Approved 8429	Lipoglutaren Approved Use Hypolipidemic

PubMed

Title	Date	PubMed
Studies on a child suspected of having a dficiency in 3-hydroxy-3-methylglutaryl-Co A lyase.	1979 Jul 2	509721
Screening newborns for multiple organic acidurias in dried filter paper urine samples: method development.	1991 Oct	1956713
Age-related reference values for urinary organic acids in a healthy Turkish pediatric population.	1994 Jun	8087979
Mitochondrial DNA depletion associated with partial complex II and IV deficiencies and 3-methylglutaconic aciduria.	2001 Feb	11292221
3-Hydroxy-3-methylglutaric aciduria in an Italian patient is caused by a new nonsense mutation in the HMGCL gene.	2001 Jul	11461194
An oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3-hydroxy-3-methyl glutaric acid residues.	2001 Oct	11576603
Immunoglobulins and cytokines level in follicular fluid in relation to etiology of infertility and their relevance to IVF outcome.	2002 Feb	11900592
3-methyglutaconic aciduria in a Chinese patient with glycogen storage disease Ib.	2003	14707520
Biochemical and molecular analyses in three patients with 3-hydroxy-3-methylglutaric aciduria.	2003	14518825
Structural (betaalpha)8 TIM barrel model of 3-hydroxy-3-methylglutaryl-coenzyme A lyase.	2003 Aug 1	12746442
Fungal metabolic model for 3-methylcrotonyl-CoA carboxylase deficiency.	2004 Feb 6	14612443
NMR spectroscopic studies on the late onset form of 3-methylglutaconic aciduria type I and other defects in leucine metabolism.	2006 Apr	16541463
A single-residue mutation, G203E, causes 3-hydroxy-3-methylglutaric aciduria by occluding the substrate channel in the 3D structural model of HMG-CoA lyase.	2006 Feb	16601870
Metabolomic and bioinformatic analyses in asphyxiated neonates.	2006 Mar	16460720
3-Methylglutaric acid as a 13C solid-state NMR standard.	2006 Oct	16887343
The chain length of lignan macromolecule from flaxseed hulls is determined by the incorporation of coumaric acid glucosides and ferulic acid glucosides.	2009 Jan	19155025
Striatum is more vulnerable to oxidative damage induced by the metabolites accumulating in 3-hydroxy-3-methylglutaryl-CoA lyase deficiency as compared to liver.	2009 Jun	19460629
Ten novel HMGCL mutations in 24 patients of different origin with 3-hydroxy-3-methyl-glutaric aciduria.	2009 Mar	19177531
[Late onset 3-HMG-CoA lyase deficiency: a rare but treatable disorder].	2010 Jan	19932602
Citrusosides A-D and furanocoumarins with cholinesterase inhibitory activity from the fruit peels of Citrus hystrix.	2010 Nov 29	20964319

Patents

Sample Use Guides

In Vivo Use Guide

Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia.

Route of Administration: Oral

In Vitro Use Guide

Meglutol (5mM) induced lipid peroxidation and decreased GSH concentrations in vitro in rat heart supernatants.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:23:01 GMT 2023` Edited by `admin` on `Fri Dec 15 15:23:01 GMT 2023`
Record UNII	CLA99KCD53
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MEGLUTOL

Official Name

English

NSC-361411

Code

English

meglutol [INN]

Common Name

English

CB-337

Code

English

3-Hydroxy-3-methylglutaric acid

Systematic Name

English

MEGLUTOL [USAN]

Common Name

English

MEGLUTOL [MI]

Common Name

English

CB 337

Code

English

MEGLUTOL [MART.]

Common Name

English

PENTANEDIOIC ACID, 3-HYDROXY-3-METHYL-

Common Name

English

Classification Tree Code System Code

WHO-ATC

C10AX05