U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C4H4O4
Molecular Weight 116.0722
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of MALEIC ACID

SMILES

OC(=O)\C=C/C(O)=O

InChI

InChIKey=VZCYOOQTPOCHFL-UPHRSURJSA-N
InChI=1S/C4H4O4/c5-3(6)1-2-4(7)8/h1-2H,(H,5,6)(H,7,8)/b2-1-

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
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

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
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
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
Disposition of [14C]velnacrine maleate in rats, dogs, and humans.
1993 Nov-Dec
[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
Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma.
1998 Nov
Neocortical neurons cultured from mice with expanded CAG repeats in the huntingtin gene: unaltered vulnerability to excitotoxins and other insults.
2003
Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.
2004 Dec
The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist.
2008 Oct 31
Quantitative morphometry of respiratory tract epithelial cells as a tool for testing chemopreventive agent efficacy.
2010 Mar
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
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
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
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 15:07:41 GMT 2023
Edited
by admin
on Fri Dec 15 15:07:41 GMT 2023
Record UNII
91XW058U2C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MALEIC ACID
EP   HSDB   II   INCI   MART.   MI   USP-RS   WHO-DD  
INCI  
Official Name English
MALEIC ACID [MART.]
Common Name English
Maleic acid [WHO-DD]
Common Name English
MALEIC ACID [MI]
Common Name English
SODIUM AUROTHIOMALATE IMPURITY A [EP IMPURITY]
Common Name English
MALEIC ACID [INCI]
Common Name English
MALEIC ACID [HSDB]
Common Name English
MALEIC ACID [USP IMPURITY]
Common Name English
NSC-25940
Code English
MALEIC ACID [EP MONOGRAPH]
Common Name English
(Z)-BUTENEDIOIC ACID
Systematic Name English
MALEIC ACID [II]
Common Name English
MALEIC ACID [USP-RS]
Common Name English
MALIC ACID IMPURITY B [EP IMPURITY]
Common Name English
cis-Butenedioic acid
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C718
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
Code System Code Type Description
RS_ITEM_NUM
1374500
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
ECHA (EC/EINECS)
203-742-5
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
RXCUI
1426330
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY RxNorm
EVMPD
SUB12134MIG
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
CHEBI
30780
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
NSC
25940
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
PUBCHEM
444266
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
MERCK INDEX
m7037
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY Merck Index
RXCUI
1426331
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
DRUG BANK
DB04299
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
FDA UNII
91XW058U2C
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
SMS_ID
100000080141
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
CHEBI
18300
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
NCI_THESAURUS
C25951
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
CAS
110-16-7
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
HSDB
666
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
MESH
C030272
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID8021517
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
DAILYMED
91XW058U2C
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
WIKIPEDIA
MALEIC ACID
Created by admin on Fri Dec 15 15:07:42 GMT 2023 , Edited by admin on Fri Dec 15 15:07:42 GMT 2023
PRIMARY
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