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 Fumaric acid

SMILES

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

InChI

InChIKey=VZCYOOQTPOCHFL-OWOJBTEDSA-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

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
Do contrast media aggravate Fanconi's syndrome in rats? A comparison of diatrizoate, iohexol, and ioxilan.
1988 Sep
Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease.
1991 Jan 2
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
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
Subcritical mineralization of sodium salt of dodecyl benzene sulfonate using sonication-wet oxidation (SONIWO) technique.
2001 Jun
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
Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles.
2004 Dec
Protein adsorption from flowing solutions on pure and maleic acid copolymer modified glass particles.
2006 Aug 1
Probing carboxylate Gibbs transfer energies via liquid|liquid transfer at triple phase boundary electrodes: ion-transfer voltammetry versus COSMO-RS predictions.
2008 Jul 14
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
Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.
2013 Jun
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
Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells.
2018 Feb
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 22:39:38 UTC 2023
Edited
by admin
on Wed Jul 05 22:39:38 UTC 2023
Record UNII
88XHZ13131
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Fumaric acid
FCC   FHFI   HSDB   II   INCI   MART.   MI   USP-RS   VANDF   WHO-DD  
INCI  
Official Name English
TRANS-BUTENEDIOIC ACID
Systematic Name English
2(TRANS)-BUTENEDIOIC ACID
Systematic Name English
BOLETIC-ACID
Common Name English
INS NO.297
Code English
SODIUM AUROTHIOMALATE IMPURITY B [EP IMPURITY]
Common Name English
FEMA NO. 2488
Code English
MALIC ACID IMPURITY A [EP IMPURITY]
Common Name English
FUMARIC ACID [MI]
Common Name English
E-297
Code English
2-BUTENEDIOIC ACID, (E)-
Common Name English
Fumaric acid [WHO-DD]
Common Name English
FUMARIC ACID [USP IMPURITY]
Common Name English
ETHYLENEDICARBOXYLIC ACID
Systematic Name English
ALLOMALEIC-ACID
Common Name English
(E)-BUTENEDIOIC ACID
Systematic Name English
FUMARIC ACID [INCI]
Common Name English
FUMARIC ACID [HSDB]
Common Name English
FUMARICUM ACIDUM [HPUS]
Common Name English
FUMARIC ACID [MART.]
Common Name English
NSC-2752
Code English
TRANS-1,2-ETHYLENEDICARBOXYLIC ACID
Common Name English
FUMARICUM ACIDUM
HPUS  
Common Name English
FUMARIC ACID [VANDF]
Common Name English
FUMARIC ACID [USP-RS]
Common Name English
FUMARIC ACID [FHFI]
Common Name English
FUMARIC ACID [II]
Common Name English
INS-297
Code English
FUMARIC ACID [FCC]
Common Name English
Classification Tree Code System Code
LOINC 13743-0
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
LOINC 25101-7
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
DSLD 1281 (Number of products:28)
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
NCI_THESAURUS C345
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
LOINC 2303-6
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
EPA PESTICIDE CODE 51201
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
WHO-VATC QD05AX01
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
LOINC 26799-7
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
CODEX ALIMENTARIUS (GSFA) INS-297
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
JECFA EVALUATION FUMARIC ACID
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
WHO-ATC D05AX01
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
CFR 21 CFR 522.84
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
LOINC 75081-0
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
JECFA EVALUATION INS-297
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL503160
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
JECFA MONOGRAPH
INS-297
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
CAS
623158-97-4
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
SUPERSEDED
DAILYMED
88XHZ13131
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
DRUG CENTRAL
3229
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
MERCK INDEX
M5586
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY Merck Index
DRUG BANK
DB01677
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
RXCUI
25389
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
SMS_ID
100000078671
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
CAS
110-17-8
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
HSDB
710
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
EVMPD
SUB13935MIG
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
FDA UNII
88XHZ13131
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
RXCUI
70598
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
ALTERNATIVE
WIKIPEDIA
FUMARIC ACID
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
CHEBI
18012
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
NSC
2752
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
EPA CompTox
DTXSID3021518
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
ECHA (EC/EINECS)
203-743-0
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
NCI_THESAURUS
C63655
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
PUBCHEM
444972
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
MESH
C032005
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
CHEBI
29806
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
RS_ITEM_NUM
1286708
Created by admin on Wed Jul 05 22:39:38 UTC 2023 , Edited by admin on Wed Jul 05 22:39:38 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
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SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
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SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> METABOLITE INACTIVE
Unit: percent of total dose excreted; Combined amount with "citric acid"
IN-VIVO
PLASMA
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
PARENT -> IMPURITY
USP
Related Record Type Details
ACTIVE MOIETY