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Details

Stereochemistry ACHIRAL
Molecular Formula C6H8O4
Molecular Weight 144.1256
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DIMETHYL FUMARATE

SMILES

COC(=O)/C(/[H])=C(\[H])/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 144.1256
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
The influence of long-term treatment with timolol on human tear lysozyme albumin content.
1982
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
Disposition of [14C]velnacrine maleate in rats, dogs, and humans.
1993 Nov-Dec
Age-related reference values for urinary organic acids in a healthy Turkish pediatric population.
1994 Jun
[Studies on the mechanisms of renal damages induced by nephrotoxic compounds].
1995 Dec
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.
1996 Dec
Glycine attenuates Fanconi syndrome induced by maleate or ifosfamide in rats.
1996 Mar
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
Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients.
1998
Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma.
1998 Nov
In vitro shear bond strength of adhesive to normal and fluoridated enamel under various contaminated conditions.
1999 Aug
Experience with intraarterial infusion of styrene maleic acid neocarzinostatin (SMANCS)-lipiodol in pancreatic cancer.
1999 Jul-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
The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy.
2002 May 15
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
Dynamic alterations of fibronectin layers on copolymer substrates with graded physicochemical characteristics.
2004 Mar 30
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
Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
2005 Oct
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
Molecular mechanisms of Nrf2-mediated antioxidant response.
2009 Feb
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
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.
2010 Oct 20
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
Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.
2014 Nov
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
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
The starting dose for TECFIDERA is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day orally. Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose. Within 4 weeks, the recommended dose of 240 mg twice a day should be resumed. Discontinuation of TECFIDERA should be considered for patients unable to tolerate return to the maintenance dose. The incidence of flushing may be reduced by administration of TECFIDERA with food. Alternatively, administration of non-enteric coated aspirin (up to a dose of 325 mg) 30 minutes prior to TECFIDERA dosing may reduce the incidence or severity of flushing.
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.
MMF did not affect endothelial cell growth when tested at 200 uM.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:06:22 UTC 2021
Edited
by admin
on Sat Jun 26 09:06:22 UTC 2021
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
DIMETHYL FUMARATE [WHO-DD]
Common Name 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
Classification Tree Code System Code
NCI_THESAURUS C29708
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
WHO-ATC N07XX09
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
NCI_THESAURUS C798
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
EU-Orphan Drug EU/3/18/1990
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
FDA ORPHAN DRUG 406713
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
WHO-ATC L04AX07
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
FDA ORPHAN DRUG 607917
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
WHO-VATC QN07XX09
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
EMA ASSESSMENT REPORTS TECFIDERA (AUTHORIZED: MULTIPLE SCLEROSIS)
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C63670
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
IUPHAR
7045
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
RXCUI
1373478
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY RxNorm
MESH
C056020
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
HSDB
7725
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
PUBCHEM
637568
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
MERCK INDEX
M11738
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB08908
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
EPA CompTox
624-49-7
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
ECHA (EC/EINECS)
210-849-0
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
EVMPD
SUB13608MIG
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
DRUG CENTRAL
4757
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
ChEMBL
CHEMBL2107333
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
WIKIPEDIA
DIMETHYL FUMARATE
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
LACTMED
Dimethyl fumarate
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
FDA UNII
FO2303MNI2
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
CAS
624-49-7
Created by admin on Sat Jun 26 09:06:22 UTC 2021 , Edited by admin on Sat Jun 26 09:06:22 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
MAJOR
Related Record Type Details
METABOLITE INACTIVE -> PARENT
Unit: percent of total dose excreted (into Expired Air; 39.7% to 58.6%)
IN-VIVO
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
IN-VIVO
URINE
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other cysteine 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 total dose excreted; Combined amount with "citric acid"
IN-VIVO
PLASMA
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with other cysteine conjugates
IN-VIVO
URINE
METABOLITE INACTIVE -> PARENT
Unit: percent of dose; Amount combined with "Fumaric Acid"
IN-VIVO
PLASMA
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