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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

Molecular Formula C6H8O4
Molecular Weight 144.1253
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Maleic acid (cis-butenedioic acid) is the cis-isomer of fumaric acid (trans-butenedioic acid). In industry, maleic acid is derived by hydrolysis of maleic anhydride, the latter being produced by oxidation of benzene or butane. Maleic acid is an industrial raw material for the production of glyoxylic acid by ozonolysis. Maleic acid is also used as an adhesion promoter for different substrates, such as nylon and zinc coated metals e.g galvanized steel, in methyl methacrylate based adhesives. The major industrial use of maleic acid is its conversion to fumaric acid. This conversion, an isomerization, is catalysed by a variety of reagents, such as mineral acids and thiourea. According to the California Environmental Protection Agency, the statewide emission rate of maleic anhydride from industrial facilities is estimated at 3340 kg/year. Maleic acid is also used as an adhesive in dentistry, as well as a fragrance ingredient and pH adjuster in many cosmetic and pharmaceutical products at low concentrations (0.004%). The large difference in water solubility makes fumaric acid purification easy. Some bacteria produce the enzyme maleate isomerase, which is used by bacteria in nicotinate metabolism. Maleic acid may be used to form acid addition salts with drugs to make them more stable. Many drugs that contain amines are provided as the maleate acid salt, e.g. carfenazine, chlorpheniramine, pyrilamine, methylergonovine, and thiethylperazine.

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

1.36434234E12
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

1.36425597E12
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
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds.
1977 Apr
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
Menstrual migraine and intermittent ergonovine therapy.
1989 Jun
Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease.
1991 Jan 2
Antifungal activity of fumaric acid in mice infected with Candida albicans.
1991 Nov
Ocular surface alteration after long-term treatment with an antiglaucomatous drug.
1992 Jul
Physiology and pathophysiology of organic acids in cerebrospinal fluid.
1993
Age-related reference values for urinary organic acids in a healthy Turkish pediatric population.
1994 Jun
Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients.
1998
In vitro shear bond strength of adhesive to normal and fluoridated enamel under various contaminated conditions.
1999 Aug
Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.
2000 Jul
Subcritical mineralization of sodium salt of dodecyl benzene sulfonate using sonication-wet oxidation (SONIWO) technique.
2001 Jun
Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate.
2002 Jul
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
Dynamic alterations of fibronectin layers on copolymer substrates with graded physicochemical characteristics.
2004 Mar 30
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
Protein adsorption from flowing solutions on pure and maleic acid copolymer modified glass particles.
2006 Aug 1
Effects of antiglaucoma drugs on collagen gel contraction mediated by human corneal fibroblasts.
2006 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
Quantitative morphometry of respiratory tract epithelial cells as a tool for testing chemopreventive agent efficacy.
2010 Mar
Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes.
2010 May
Structure-activity comparison of the cytotoxic properties of diethyl maleate and related molecules: identification of diethyl acetylenedicarboxylate as a thiol cross-linking agent.
2011 Jan 14
Fumaric acid attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling.
2013 Aug
Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.
2013 Jun
Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells.
2013 Oct
Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells.
2017
Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate.
2017
Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model.
2017 Dec
Bioanalysis of monomethyl fumarate in human plasma by a sensitive and rapid LC-MS/MS method and its pharmacokinetic application.
2017 Nov 30
Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium.
2018 Dec
Dimethyl fumarate treatment alters NK cell function in multiple sclerosis.
2018 Feb
Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells.
2018 Feb
Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis.
2018 Jan
Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells.
2019 Jan
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
in cow: The aim of this study was to determine the influence of fumaric acid (FA) on ruminal fermentation and its effects on the acid-base balance of seven ruminally and duodenally fistulated multiparous German Holstein cows. The experiment was conducted in a change-over design with three periods in which the animals were randomly arranged in one of three treatments: Control (C; without FA), 300 or 600 g FA per day. The diets consisted of 7.4 kg DM grass silage, 4.2 kg concentrate mixture and 0, 300 or 600 g FA or wheat starch as isocaloric compensation per day and cow. FA supplementation decreased the rumen pH, acetic acid and butyric acid and increased propionic acid in rumen fluid. The results of the single-strand conformation polymorphism analysis (SSCP) did not show an influence of FA on the microbial population in the rumen
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.
It was evaluated the effects of fumaric acid (FA) on tyrosinase activity and structure via enzyme kinetics and computational simulations. FA was found to be a reversible inhibitor of tyrosinase and its induced mechanism was the parabolic non-competitive inhibition type with IC50=13.7±0.25mM and Kislope=12.64±0.75mM. Kinetic measurements and spectrofluorimetry studies showed that FA induced regional changes in the active site of tyrosinase. One possible binding site for FA was identified under the condition without L-DOPA. The computational docking simulations further revealed that FA can interact with HIS263 and HIS85 at the active site. Furthermore, four important hydrogen bonds were found to be involved with the docking of FA on tyrosinase. By inhibiting tyrosinase and its central role in pigment production, FA is a potential natural antipigmentation agent.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:36:27 UTC 2023
Edited
by admin
on Wed Jul 05 23:36:27 UTC 2023
Record UNII
FO2303MNI2
Record Status Validated (UNII)
Record Version
  • Download
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 Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
WHO-ATC N07XX09
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
NCI_THESAURUS C798
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
EU-Orphan Drug EU/3/18/1990
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
FDA ORPHAN DRUG 406713
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
WHO-ATC L04AX07
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
FDA ORPHAN DRUG 607917
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
WHO-VATC QN07XX09
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
EMA ASSESSMENT REPORTS TECFIDERA (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C63670
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
IUPHAR
7045
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
NSC
25942
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
RXCUI
1373478
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY RxNorm
MESH
C056020
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
USAN
QQ-86
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
HSDB
7725
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
PUBCHEM
637568
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
MERCK INDEX
M11738
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY Merck Index
CHEBI
76004
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
DRUG BANK
DB08908
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID4060787
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
SMS_ID
100000079228
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
ECHA (EC/EINECS)
210-849-0
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
EVMPD
SUB13608MIG
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
DRUG CENTRAL
4757
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
ChEMBL
CHEMBL2107333
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
WIKIPEDIA
DIMETHYL FUMARATE
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
LACTMED
Dimethyl fumarate
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
FDA UNII
FO2303MNI2
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
CAS
624-49-7
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
DAILYMED
FO2303MNI2
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
NSC
167432
Created by admin on Wed Jul 05 23:36:27 UTC 2023 , Edited by admin on Wed Jul 05 23:36:27 UTC 2023
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
MAJOR
Related Record Type Details
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other cysteine conjugates
IN-VIVO
URINE
METABOLITE INACTIVE -> PARENT
Unit: percent of total dose excreted; Combined amount with "citric acid"
IN-VIVO
PLASMA
METABOLITE INACTIVE -> PARENT
Unit: percent of dose
IN-VIVO
URINE
METABOLITE ACTIVE -> PARENT
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other N-acetylcysteine conjugates
IN-VIVO
URINE
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other N-acetylcysteine conjugates
IN-VIVO
URINE
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with "Fumaric Acid"
IN-VIVO
PLASMA
METABOLITE INACTIVE -> PARENT
Unit: percent of total dose excreted (into Expired Air; 39.7% to 58.6%)
IN-VIVO
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other cysteine conjugates
IN-VIVO
URINE
Related Record Type Details
ACTIVE MOIETY
Dimethyl fumarate is highly reactive: when administered orally, it does not survive long enough to be absorbed into blood without being attacked by GSH (detoxifying agent). However, part of it is hydrolyzed by esterases to produce monomethylfumarate, which is more resistant