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Details

Stereochemistry ACHIRAL
Molecular Formula C5H6O4
Molecular Weight 130.0989
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of MONOMETHYL FUMARATE

SMILES

COC(=O)/C(/[H])=C(\[H])/C(=O)O

InChI

InChIKey=NKHAVTQWNUWKEO-NSCUHMNNSA-N
InChI=1S/C5H6O4/c1-9-5(8)3-2-4(6)7/h2-3H,1H3,(H,6,7)/b3-2+

HIDE SMILES / InChI

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
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
Do contrast media aggravate Fanconi's syndrome in rats? A comparison of diatrizoate, iohexol, and ioxilan.
1988 Sep
Menstrual migraine and intermittent ergonovine therapy.
1989 Jun
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
Morphological effect of the type, concentration and etching time of acid solutions on enamel and dentin surfaces.
1998
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
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
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
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
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
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.
2010 Oct 20
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
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
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
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.
Name Type Language
MONOMETHYL FUMARATE
USAN   INN  
Official Name English
METHYL HYDROGEN FUMARATE
Systematic Name English
MONOMETHYL FUMARATE [USAN]
Common Name English
NSC-523835
Code English
MMF
Common Name English
FUMARIC ACID MONOMETHYL ESTER [MI]
Common Name English
FUMARIC ACID MONOMETHYL ESTER
MI  
Systematic Name English
MONOMETHYL FUMARATE [WHO-DD]
Common Name English
MONOMETHYL FUMARATE [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 724619
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
Code System Code Type Description
PUBCHEM
5369209
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
RXCUI
1546433
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
220-412-6
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
NCI_THESAURUS
C166722
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
CAS
2756-87-8
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
INN
11163
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
DRUG BANK
DB14219
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
EVMPD
SUB184027
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
FDA UNII
45IUB1PX8R
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY
MERCK INDEX
M5586
Created by admin on Fri Jun 25 21:58:06 UTC 2021 , Edited by admin on Fri Jun 25 21:58:06 UTC 2021
PRIMARY Merck Index