Details
Stereochemistry | ACHIRAL |
Molecular Formula | C5H6O4 |
Molecular Weight | 130.0987 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC(=O)\C=C\C(O)=O
InChI
InChIKey=NKHAVTQWNUWKEO-NSCUHMNNSA-N
InChI=1S/C5H6O4/c1-9-5(8)3-2-4(6)7/h2-3H,1H3,(H,6,7)/b3-2+
Molecular Formula | C5H6O4 |
Molecular Weight | 130.0987 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/15987702 | https://www.ncbi.nlm.nih.gov/pubmed/17182618https://www.ncbi.nlm.nih.gov/pubmed/12522577 | https://www.ncbi.nlm.nih.gov/pubmed/27614618 | https://www.ncbi.nlm.nih.gov/pubmed/20664170 | https://multiplesclerosisnewstoday.com/alks-8700-multiple-sclerosis/http://onlinelibrary.wiley.com/doi/10.1002/047084289X.rd344/fullhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdfhttp://www.google.ru/patents/US3887480 | https://www.google.com/patents/US4668735https://www.ncbi.nlm.nih.gov/pubmed/28340950Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20647102 | https://www.ncbi.nlm.nih.gov/pubmed/19595601
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15987702 | https://www.ncbi.nlm.nih.gov/pubmed/17182618https://www.ncbi.nlm.nih.gov/pubmed/12522577 | https://www.ncbi.nlm.nih.gov/pubmed/27614618 | https://www.ncbi.nlm.nih.gov/pubmed/20664170 | https://multiplesclerosisnewstoday.com/alks-8700-multiple-sclerosis/http://onlinelibrary.wiley.com/doi/10.1002/047084289X.rd344/fullhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdfhttp://www.google.ru/patents/US3887480 | https://www.google.com/patents/US4668735https://www.ncbi.nlm.nih.gov/pubmed/28340950
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/20647102 | https://www.ncbi.nlm.nih.gov/pubmed/19595601
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28832396http://www.ncbi.nlm.nih.gov/pubmed/25725349
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
Sources: http://adisinsight.springer.com/drugs/800038403http://pubs.rsc.org/en/content/articlehtml/1925/CT/CT9252701868http://www.ncbi.nlm.nih.gov/pubmed/15991882
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL6182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19595601 |
|||
Target ID: Q96KS0 Gene ID: 112398.0 Gene Symbol: EGLN2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17182618 |
120.0 µM [IC50] | ||
Target ID: Q9H6Z9 Gene ID: 112399.0 Gene Symbol: EGLN3 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17182618 |
60.0 µM [IC50] | ||
Target ID: Q9GZT9 Gene ID: 54583.0 Gene Symbol: EGLN1 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/17182618 |
80.0 µM [IC50] | ||
Target ID: WP2884 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27614618 |
|||
Target ID: GO:0070269 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26096886 |
|||
Target ID: CHEMBL4420 |
|||
Target ID: Q16236 Gene ID: 4780.0 Gene Symbol: NFE2L2 Target Organism: Homo sapiens (Human) |
|||
Target ID: Glutathione S-transferase Sources: https://www.ncbi.nlm.nih.gov/pubmed/1287182 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Diagnostic | Unknown Approved UseUnknown |
|||
Secondary | TECFIDERA Approved UseIndicated for the treatment of patients with relapsing forms of multiple sclerosis Launch Date1.36434234E12 |
|||
Palliative | Unknown Approved UseUnknown |
|||
Primary | TECFIDERA Approved UseTECFIDERA, 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 Date1.36425597E12 |
|||
Preventing | Unknown Approved UseUnknown |
|||
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
Antifungal properties of 2-bromo-3-fluorosuccinic acid esters and related compounds. | 1977 Apr |
|
The influence of long-term treatment with timolol on human tear lysozyme albumin content. | 1982 |
|
Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis. | 1986 Mar |
|
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 |
|
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 |
|
The comparison of plasma deproteinization methods for the detection of low-molecular-weight metabolites by (1)H nuclear magnetic resonance spectroscopy. | 2002 May 15 |
|
Dynamic alterations of fibronectin layers on copolymer substrates with graded physicochemical characteristics. | 2004 Mar 30 |
|
Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats. | 2005 Aug 15 |
|
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 |
|
Small molecule activators of the Nrf2-HO-1 antioxidant axis modulate heme metabolism and inflammation in BV2 microglia cells. | 2013 Oct |
|
Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I. | 2014 Nov |
|
Monomethyl fumarate inhibits pain behaviors and amygdala activity in a rat arthritis model. | 2017 Dec |
|
Monomethyl fumarate treatment impairs maturation of human myeloid dendritic cells and their ability to activate T cells. | 2019 Jan |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24313964
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27940340
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
Edited
Thu Jul 06 01:21:58 UTC 2023
by
admin
on
Thu Jul 06 01:21:58 UTC 2023
|
Record UNII |
45IUB1PX8R
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
724619
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
Monomethyl fumarate
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
5369209
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
1546433
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | RxNorm | ||
|
220-412-6
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
C166722
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
2756-87-8
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
11163
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
100000170158
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
DB14219
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
167450
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
DTXSID801016498
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
SUB184027
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
1210229
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
FG-183
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
45IUB1PX8R
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
45IUB1PX8R
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
523835
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | |||
|
M5586
Created by
admin on Thu Jul 06 01:21:59 UTC 2023 , Edited by admin on Thu Jul 06 01:21:59 UTC 2023
|
PRIMARY | Merck Index |
Related Record | Type | Details | ||
---|---|---|---|---|
|
BINDER->LIGAND |
BINDING
|
||
|
TARGET -> ACTIVATOR |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
PRODRUG -> METABOLITE ACTIVE | |||
|
METABOLITE -> PARENT |
MAJOR
EXHALATION
|
||
|
PARENT -> METABOLITE ACTIVE | |||
|
PRODRUG -> METABOLITE ACTIVE |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
---|---|---|---|---|---|---|
Volume of Distribution | PHARMACOKINETIC |
|
|
|||
Biological Half-life | PHARMACOKINETIC |
|
|
|||