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Details

Stereochemistry ACHIRAL
Molecular Formula C11H17NO5
Molecular Weight 243.2564
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of TEPILAMIDE FUMARATE

SMILES

CCN(CC)C(=O)COC(=O)\C=C\C(=O)OC

InChI

InChIKey=AKUGRXRLHCCENI-VOTSOKGWSA-N
InChI=1S/C11H17NO5/c1-4-12(5-2)9(13)8-17-11(15)7-6-10(14)16-3/h6-7H,4-5,8H2,1-3H3/b7-6+

HIDE SMILES / InChI

Molecular Formula C11H17NO5
Molecular Weight 243.2564
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
Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis.
1986 Mar
Antifungal activity of fumaric acid in mice infected with Candida albicans.
1991 Nov
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
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.
1996 Dec
Morphological effect of the type, concentration and etching time of acid solutions on enamel and dentin surfaces.
1998
Experience with intraarterial infusion of styrene maleic acid neocarzinostatin (SMANCS)-lipiodol in pancreatic cancer.
1999 Jul-Aug
An in vitro study on restoring bond strength of a GIC to saliva contaminated enamel under unrinse condition.
2002 Jul-Aug
The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy.
2002 May 15
Aqueous humour flow after a single oral dose of isosorbide-5-mononitrate in healthy volunteers.
2003 Aug
Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells.
2005 Feb
Determination of ergometrine maleate by fluorescence detection.
2005 May-Jun
Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate.
2005 Oct
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
DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1.
2010 Oct 20
Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.
2013 Jun
Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells.
2017
Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium.
2018 Dec
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 Thu Jul 06 12:08:29 UTC 2023
Edited
by admin
on Thu Jul 06 12:08:29 UTC 2023
Record UNII
KOS9TZ09CM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TEPILAMIDE FUMARATE
USAN   INN  
Official Name English
PPC-06
Code English
2-(Diethylamino)-2-oxoethyl and methyl (2E)-but-2-enedioate
Systematic Name English
XP23829
Code English
Tepilamide fumarate [WHO-DD]
Common Name English
XP-23829
Code English
2-BUTENEDIOIC ACID (2E)-, 1-(2-(DIETHYLAMINO)-2-OXOETHYL) 4-METHYL ESTER
Systematic Name English
(N,N-DIETHYLCARBAMOYL)METHYL METHYL (2E)-BUT-2-ENE-1,4-DIOATE
Systematic Name English
tepilamide fumarate [INN]
Common Name English
TEPILAMIDE FUMARATE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C308
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C152564
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
USAN
CD-184
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
INN
10672
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
FDA UNII
KOS9TZ09CM
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
CAS
1208229-58-6
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
SMS_ID
100000181193
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
PUBCHEM
46179632
Created by admin on Thu Jul 06 12:08:29 UTC 2023 , Edited by admin on Thu Jul 06 12:08:29 UTC 2023
PRIMARY
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METABOLITE ACTIVE -> PRODRUG
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ACTIVE MOIETY