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Details

Stereochemistry ACHIRAL
Molecular Formula C11H13NO6
Molecular Weight 255.224
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DIROXIMEL FUMARATE

SMILES

COC(=O)\C=C\C(=O)OCCN1C(=O)CCC1=O

InChI

InChIKey=YIMYDTCOUQIDMT-SNAWJCMRSA-N
InChI=1S/C11H13NO6/c1-17-10(15)4-5-11(16)18-7-6-12-8(13)2-3-9(12)14/h4-5H,2-3,6-7H2,1H3/b5-4+

HIDE SMILES / InChI

Molecular Formula C11H13NO6
Molecular Weight 255.224
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
Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid.
1985 Jun
Do contrast media aggravate Fanconi's syndrome in rats? A comparison of diatrizoate, iohexol, and ioxilan.
1988 Sep
[Studies on the mechanisms of renal damages induced by nephrotoxic compounds].
1995 Dec
Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC.
2000 Jul
An in vitro study on restoring bond strength of a GIC to saliva contaminated enamel under unrinse condition.
2002 Jul-Aug
Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats.
2005 Aug 15
Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
2005 Oct
Probing carboxylate Gibbs transfer energies via liquid|liquid transfer at triple phase boundary electrodes: ion-transfer voltammetry versus COSMO-RS predictions.
2008 Jul 14
Quantitative morphometry of respiratory tract epithelial cells as a tool for testing chemopreventive agent efficacy.
2010 Mar
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.
2010 Oct 20
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 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 Sat Dec 16 11:38:15 GMT 2023
Edited
by admin
on Sat Dec 16 11:38:15 GMT 2023
Record UNII
K0N0Z40J3W
Record Status Validated (UNII)
Record Version
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Name Type Language
DIROXIMEL FUMARATE
INN   USAN  
INN   USAN  
Official Name English
diroximel fumarate [INN]
Common Name English
DIROXIMEL FUMARATE [USAN]
Common Name English
DIROXIMEL FUMARATE [ORANGE BOOK]
Common Name English
ALKS8700
Code English
BIIB-098
Code English
BIIB098
Code English
DIROXIMEL FUMARATE [MI]
Common Name English
VUMERITY
Brand Name English
2-BUTENEDIOIC ACID (2E)-, 1-(2-(2,5-DIOXO-1-PYRROLIDINYL)ETHYL) 4-METHYL ESTER
Systematic Name English
RDC5108
Code English
2-(2,5-Dioxopyrrolidin-1-yl)ethyl methyl (2E)-but-2-enedioate
Systematic Name English
Diroximel fumarate [WHO-DD]
Common Name English
RDC-5108
Code English
ALKS-8700
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 724719
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
Code System Code Type Description
RXCUI
2261783
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
NCI_THESAURUS
C169916
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
DAILYMED
K0N0Z40J3W
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
INN
10356
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
SMS_ID
100000174626
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
WIKIPEDIA
Diroximel fumarate
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
MERCK INDEX
m12236
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
DRUG BANK
DB14783
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
USAN
DE-126
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
PUBCHEM
73330464
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
EPA CompTox
DTXSID101026181
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
CAS
1577222-14-0
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
FDA UNII
K0N0Z40J3W
Created by admin on Sat Dec 16 11:38:15 GMT 2023 , Edited by admin on Sat Dec 16 11:38:15 GMT 2023
PRIMARY
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