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

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
Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid.
1985 Jun
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
Ocular surface alteration after long-term treatment with an antiglaucomatous drug.
1992 Jul
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
[Studies on the mechanisms of renal damages induced by nephrotoxic compounds].
1995 Dec
Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients.
1998
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
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
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
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
Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells.
2018 Feb
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 22:39:36 UTC 2023
Edited
by admin
on Wed Jul 05 22:39:36 UTC 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 Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
Code System Code Type Description
RS_ITEM_NUM
1374500
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
ECHA (EC/EINECS)
203-742-5
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
RXCUI
1426330
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY RxNorm
EVMPD
SUB12134MIG
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
CHEBI
30780
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
NSC
25940
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
PUBCHEM
444266
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
MERCK INDEX
M7037
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY Merck Index
RXCUI
1426331
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
DRUG BANK
DB04299
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
FDA UNII
91XW058U2C
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
SMS_ID
100000080141
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
CHEBI
18300
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
NCI_THESAURUS
C25951
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
CAS
110-16-7
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
HSDB
666
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
MESH
C030272
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
EPA CompTox
DTXSID8021517
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
DAILYMED
91XW058U2C
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
WIKIPEDIA
MALEIC ACID
Created by admin on Wed Jul 05 22:39:36 UTC 2023 , Edited by admin on Wed Jul 05 22:39:36 UTC 2023
PRIMARY
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