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Details

Stereochemistry ACHIRAL
Molecular Formula C6H8O4
Molecular Weight 144.1253
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DIMETHYL FUMARATE

SMILES

COC(=O)\C=C\C(=O)OC

InChI

InChIKey=LDCRTTXIJACKKU-ONEGZZNKSA-N
InChI=1S/C6H8O4/c1-9-5(7)3-4-6(8)10-2/h3-4H,1-2H3/b4-3+

HIDE SMILES / InChI
Dimethyl maleate is an organic compound, the (Z)-isomer of the dimethyl ester of fumaric acid. Dimethyl maleate can be synthesized from maleic anhydride and methanol, with sulfuric acid acting as acid catalyst, via a nucleophilic acyl substitution for the monomethyl ester, followed by a Fischer esterification reaction for the dimethyl ester. Dimethyl maleate is used in many organic syntheses as a dienophile for diene synthesis. It is used as an additive and intermediate for plastics, pigments, pharmaceuticals, and agricultural products. It is also an intermediate for the production of paints, adhesives, and copolymers.

CNS Activity

Curator's Comment: Dimethyl fumarate is probably too hydrophilic to cross the blood-CNS barrier. DMF stabilized the BBB by preventing disruption of interendothelial tight junctions and gap formation, and decreased matrix metalloproteinase activity in brain tissue.

Originator

Curator's Comment: In September 2003, Biogen (now Biogen Idec) licensed exclusive worldwide rights (excluding Germany) from Fumapharm to develop and market BG 12.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q96KS0
Gene ID: 112398.0
Gene Symbol: EGLN2
Target Organism: Homo sapiens (Human)
120.0 µM [IC50]
Target ID: Q9H6Z9
Gene ID: 112399.0
Gene Symbol: EGLN3
Target Organism: Homo sapiens (Human)
60.0 µM [IC50]
Target ID: Q9GZT9
Gene ID: 54583.0
Gene Symbol: EGLN1
Target Organism: Homo sapiens (Human)
80.0 µM [IC50]
Target ID: Glutathione S-transferase
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Diagnostic
Unknown

Approved Use

Unknown
Secondary
TECFIDERA

Approved Use

Indicated for the treatment of patients with relapsing forms of multiple sclerosis

Launch Date

2013
Palliative
Unknown

Approved Use

Unknown
Primary
TECFIDERA

Approved Use

TECFIDERA, dimethyl fumarate undergoes rapid presystemic hydrolysis by esterases and is converted to its active metabolite, monomethyl fumarate (MMF). TECFIDERA is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

Launch Date

2013
Preventing
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.87 mg/L
240 mg 2 times / day multiple, oral
dose: 240 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MONOMETHYL FUMARATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
8.21 mg × h/L
240 mg 2 times / day multiple, oral
dose: 240 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MONOMETHYL FUMARATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1 h
240 mg 2 times / day multiple, oral
dose: 240 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MONOMETHYL FUMARATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
64%
240 mg 2 times / day multiple, oral
dose: 240 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
MONOMETHYL FUMARATE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
190 mg 2 times / day multiple, oral
Highest studied dose
Dose: 190 mg, 2 times / day
Route: oral
Route: multiple
Dose: 190 mg, 2 times / day
Sources: Page: 6.1
unhealthy, adult
n = 769
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: adult
Sex: unknown
Population Size: 769
Sources: Page: 6.1
190 mg 2 times / day multiple, oral
Highest studied dose
Dose: 190 mg, 2 times / day
Route: oral
Route: multiple
Dose: 190 mg, 2 times / day
Sources:
unhealthy, mean 37 years
n = 105
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: mean 37 years
Sex: M+F
Population Size: 105
Sources:
Other AEs: Gastrointestinal disturbance...
Other AEs:
Gastrointestinal disturbance (53%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disturbance 53%
190 mg 2 times / day multiple, oral
Highest studied dose
Dose: 190 mg, 2 times / day
Route: oral
Route: multiple
Dose: 190 mg, 2 times / day
Sources:
unhealthy, mean 37 years
n = 105
Health Status: unhealthy
Condition: multiple sclerosis
Age Group: mean 37 years
Sex: M+F
Population Size: 105
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid.
1985 Jun
Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis.
1986 Mar
Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease.
1991 Jan 2
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.
1996 Dec
A synthetic polycation, a copolymer of 1-vinyl-3-methylimidazole iodide with maleic acid diethyl ester, increases passive ionic permeability in erythrocyte membranes modified by fatty acids.
1998
An in vitro study on restoring bond strength of a GIC to saliva contaminated enamel under unrinse condition.
2002 Jul-Aug
Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults.
2003
Aqueous humour flow after a single oral dose of isosorbide-5-mononitrate in healthy volunteers.
2003 Aug
Molecular machinery for non-vesicular trafficking of ceramide.
2003 Dec 18
Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.
2004 Dec
Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats.
2005 Aug 15
Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.
2005 Feb
Determination of ergometrine maleate by fluorescence detection.
2005 May-Jun
Probing carboxylate Gibbs transfer energies via liquid|liquid transfer at triple phase boundary electrodes: ion-transfer voltammetry versus COSMO-RS predictions.
2008 Jul 14
The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.
2008 Oct 31
Molecular mechanisms of Nrf2-mediated antioxidant response.
2009 Feb
Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes.
2010 May
Bioanalysis of monomethyl fumarate in human plasma by a sensitive and rapid LC-MS/MS method and its pharmacokinetic application.
2017 Nov 30
Patents

Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: In group of dogs experimental Fanconi syndrome (generalized proximal tubular dysfunction) was induced with maleic acid (25 mg/kg iv, pH 7.3). https://www.ncbi.nlm.nih.gov/pubmed/1858895
462 mg twice daily
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: Maleic acid-induced inhibition of sugar and amino acid transport in the rat renal tubule was studied.
NK cells from healthy controls were treated with 10 and 100 uM of monomethyl fumarate for 12 hours then washed and co-cultured for 24 hours at 1:5 E:T ratio with or without autologous labeled T cells. Using CD107a expression to measure NK cell degranulation, is was noted an increase in the proportion of degranulated NK cells following treatment with different monomethyl fumarate concentrations. These changes occurred without dramatic effects on NK cell viability.
Name Type Language
DIMETHYL FUMARATE
DASH   HSDB   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
FAG-201
Code English
NSC-167432
Code English
BG-00012
Code English
BG 12
Code English
2-BUTENEDIOIC ACID, (2E)-, DIMETHYL ESTER
Common Name English
FP187
Code English
DIMETHYL FUMARATE [JAN]
Common Name English
BG00012
Code English
DIMETHYL FUMARATE [MI]
Common Name English
LAS-41008
Code English
DIMETHYL FUMARATE [ORANGE BOOK]
Common Name English
AZL-O-211089
Code English
LAS41008
Code English
BG 00012
Code English
DIMETHYL FUMARATE [HSDB]
Common Name English
DIMETHYL FUMARATE [USAN]
Common Name English
FUMARIC ACID DIMETHYL ESTER
MI  
Systematic Name English
NSC-25942
Code English
TECFIDERA
Brand Name English
FP-187
Code English
AZL O 211089
Code English
BG-12
Code English
PANACLAR
Brand Name English
DIMETHYL FUMARATE [VANDF]
Common Name English
Dimethyl (2E)-but-2-enedioate
Systematic Name English
AZL-0211089
Code English
Dimethyl fumarate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29708
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
WHO-ATC N07XX09
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
NCI_THESAURUS C798
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
EU-Orphan Drug EU/3/18/1990
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
FDA ORPHAN DRUG 406713
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
WHO-ATC L04AX07
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
FDA ORPHAN DRUG 607917
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
WHO-VATC QN07XX09
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
EMA ASSESSMENT REPORTS TECFIDERA (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C63670
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
IUPHAR
7045
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
NSC
25942
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
RXCUI
1373478
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY RxNorm
MESH
C056020
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
USAN
QQ-86
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
HSDB
7725
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
PUBCHEM
637568
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
MERCK INDEX
m11738
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY Merck Index
CHEBI
76004
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
DRUG BANK
DB08908
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
EPA CompTox
DTXSID4060787
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
SMS_ID
100000079228
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
ECHA (EC/EINECS)
210-849-0
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
EVMPD
SUB13608MIG
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
DRUG CENTRAL
4757
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
ChEMBL
CHEMBL2107333
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
WIKIPEDIA
DIMETHYL FUMARATE
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
LACTMED
Dimethyl fumarate
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
FDA UNII
FO2303MNI2
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY
CAS
624-49-7
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
DAILYMED
FO2303MNI2
Created by admin on Fri Dec 15 16:08:48 GMT 2023 , Edited by admin on Fri Dec 15 16:08:48 GMT 2023
PRIMARY
NSC
167432
Created by admin on Fri Dec 15 16:08:49 GMT 2023 , Edited by admin on Fri Dec 15 16:08:49 GMT 2023
PRIMARY