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Details

Stereochemistry ACHIRAL
Molecular Formula C5H6O4
Molecular Weight 130.0987
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of Monomethyl Fumarate

SMILES

COC(=O)\C=C\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

Molecular Formula C5H6O4
Molecular Weight 130.0987
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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

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
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
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
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
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
An in vitro study on restoring bond strength of a GIC to saliva contaminated enamel under unrinse condition.
2002 Jul-Aug
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
Integration of metabolomics and transcriptomics data to aid biomarker discovery in type 2 diabetes.
2010 May
Fumaric acid attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling.
2013 Aug
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
Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model.
2017 Dec
Dimethyl fumarate treatment alters NK cell function in multiple sclerosis.
2018 Feb
Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis.
2018 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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 18:05:39 UTC 2023
Edited
by admin
on Fri Dec 15 18:05:39 UTC 2023
Record UNII
45IUB1PX8R
Record Status Validated (UNII)
Record Version
  • Download
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 [ORANGE BOOK]
Common Name English
monomethyl fumarate [INN]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 724619
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
Code System Code Type Description
WIKIPEDIA
Monomethyl fumarate
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
PUBCHEM
5369209
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
RXCUI
1546433
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY RxNorm
ECHA (EC/EINECS)
220-412-6
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
NCI_THESAURUS
C166722
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
CAS
2756-87-8
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
INN
11163
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
SMS_ID
100000170158
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
DRUG BANK
DB14219
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
CHEBI
167450
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
EPA CompTox
DTXSID801016498
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
EVMPD
SUB184027
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
RS_ITEM_NUM
1210229
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
USAN
FG-183
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
DAILYMED
45IUB1PX8R
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
FDA UNII
45IUB1PX8R
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
NSC
523835
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY
MERCK INDEX
m5586
Created by admin on Fri Dec 15 18:05:39 UTC 2023 , Edited by admin on Fri Dec 15 18:05:39 UTC 2023
PRIMARY Merck Index
Related Record Type Details
BINDER->LIGAND
BINDING
TARGET -> ACTIVATOR
Related Record Type Details
PRODRUG -> METABOLITE ACTIVE
METABOLITE -> PARENT
MAJOR
EXHALATION
PRODRUG -> METABOLITE ACTIVE
PARENT -> METABOLITE ACTIVE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC