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

Details

Stereochemistry ACHIRAL
Molecular Formula C4H4O4
Molecular Weight 116.0723
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of MALEIC ACID

SMILES

C(\[H])(=C(\[H])/C(=O)O)/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 116.0723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
The influence of long-term treatment with timolol on human tear lysozyme albumin content.
1982
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
Ocular surface alteration after long-term treatment with an antiglaucomatous drug.
1992 Jul
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
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
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
Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.
2000 Jul
Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate.
2002 Jul
Molecular machinery for non-vesicular trafficking of ceramide.
2003 Dec 18
Determination of ergometrine maleate by fluorescence detection.
2005 May-Jun
Molecular mechanisms of Nrf2-mediated antioxidant response.
2009 Feb
Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.
2013 Jun
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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:16:29 UTC 2021
Edited
by admin
on Fri Jun 25 21:16:29 UTC 2021
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 [MI]
Common Name English
MALEIC ACID [INCI]
Common Name English
MALEIC ACID [HSDB]
Common Name English
MALIC ACID IMPURITY B [EP]
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
MALEIC ACID [WHO-DD]
Common Name English
CIS-BUTENEDIOIC ACID
Systematic Name English
MALEIC ACID [USP]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C718
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
Code System Code Type Description
USP_CATALOG
1374500
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY USP-RS
ECHA (EC/EINECS)
203-742-5
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
RXCUI
1426330
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY RxNorm
EVMPD
SUB12134MIG
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
PUBCHEM
444266
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
MERCK INDEX
M7037
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY Merck Index
RXCUI
1426331
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
DRUG BANK
DB04299
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
FDA UNII
91XW058U2C
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
NCI_THESAURUS
C25951
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
CAS
110-16-7
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
HSDB
666
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
MESH
C030272
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
EPA CompTox
110-16-7
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
WIKIPEDIA
MALEIC ACID
Created by admin on Fri Jun 25 21:16:30 UTC 2021 , Edited by admin on Fri Jun 25 21:16:30 UTC 2021
PRIMARY
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