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
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-
DescriptionSources: https://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/https://www.ncbi.nlm.nih.gov/pubmed/15987702 | https://www.ncbi.nlm.nih.gov/pubmed/17182618https://www.ncbi.nlm.nih.gov/pubmed/28340950http://www.google.ru/patents/US3887480 | https://www.google.com/patents/US4668735http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdfhttp://onlinelibrary.wiley.com/doi/10.1002/047084289X.rd344/fullCurator'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/12522577 | https://www.ncbi.nlm.nih.gov/pubmed/27614618 | https://www.ncbi.nlm.nih.gov/pubmed/20664170 | https://multiplesclerosisnewstoday.com/alks-8700-multiple-sclerosis/https://www.ncbi.nlm.nih.gov/pubmed/15987702 | https://www.ncbi.nlm.nih.gov/pubmed/17182618https://www.ncbi.nlm.nih.gov/pubmed/28340950http://www.google.ru/patents/US3887480 | https://www.google.com/patents/US4668735http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204063s014lbl.pdfhttp://onlinelibrary.wiley.com/doi/10.1002/047084289X.rd344/full
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
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
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://www.ncbi.nlm.nih.gov/pubmed/15991882http://pubs.rsc.org/en/content/articlehtml/1925/CT/CT9252701868
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 |
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Target ID: CHEMBL6182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19595601 |
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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 |
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Target ID: GO:0070269 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26096886 |
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Target ID: CHEMBL4420 |
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Target ID: Q16236 Gene ID: 4780.0 Gene Symbol: NFE2L2 Target Organism: Homo sapiens (Human) |
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Target ID: Glutathione S-transferase Sources: https://www.ncbi.nlm.nih.gov/pubmed/1287182 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Diagnostic | Unknown Approved UseUnknown |
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Secondary | TECFIDERA Approved UseIndicated for the treatment of patients with relapsing forms of multiple sclerosis Launch Date2013 |
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Palliative | Unknown Approved UseUnknown |
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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 Date2013 |
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Preventing | Unknown Approved UseUnknown |
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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 |
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Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis. | 1986 Mar |
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Menstrual migraine and intermittent ergonovine therapy. | 1989 Jun |
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Automated screening of urine samples for carbohydrates, organic and amino acids after treatment with urease. | 1991 Jan 2 |
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Antifungal activity of fumaric acid in mice infected with Candida albicans. | 1991 Nov |
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Ocular surface alteration after long-term treatment with an antiglaucomatous drug. | 1992 Jul |
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[Studies on the mechanisms of renal damages induced by nephrotoxic compounds]. | 1995 Dec |
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Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro. | 1996 Dec |
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Glycine attenuates Fanconi syndrome induced by maleate or ifosfamide in rats. | 1996 Mar |
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Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients. | 1998 |
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Morphological effect of the type, concentration and etching time of acid solutions on enamel and dentin surfaces. | 1998 |
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Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma. | 1998 Nov |
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In vitro shear bond strength of adhesive to normal and fluoridated enamel under various contaminated conditions. | 1999 Aug |
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Experience with intraarterial infusion of styrene maleic acid neocarzinostatin (SMANCS)-lipiodol in pancreatic cancer. | 1999 Jul-Aug |
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Determination of trimebutine and desmethyl-trimebutine in human plasma by HPLC. | 2000 Jul |
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Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate. | 2002 Jul |
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An in vitro study on restoring bond strength of a GIC to saliva contaminated enamel under unrinse condition. | 2002 Jul-Aug |
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Molecular machinery for non-vesicular trafficking of ceramide. | 2003 Dec 18 |
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Identification of anti-inflammatory drugs according to their capacity to suppress type-1 and type-2 T cell profiles. | 2004 Dec |
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Effect of inducers of DT-diaphorase on the haemolytic activity and nephrotoxicity of 2-amino-1,4-naphthoquinone in rats. | 2005 Aug 15 |
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Enhanced cytotoxicity of bioreductive antitumor agents with dimethyl fumarate in human glioblastoma cells. | 2005 Feb |
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Tumor-necrosis-factor-related apoptosis-inducing-ligand (TRAIL)-mediated death of neurons in living human brain tissue is inhibited by flupirtine-maleate. | 2005 Oct |
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Effects of antiglaucoma drugs on collagen gel contraction mediated by human corneal fibroblasts. | 2006 Jun |
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The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. | 2008 Oct 31 |
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Molecular mechanisms of Nrf2-mediated antioxidant response. | 2009 Feb |
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DMF inhibits PDGF-BB induced airway smooth muscle cell proliferation through induction of heme-oxygenase-1. | 2010 Oct 20 |
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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 |
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Fumaric acid attenuates the eotaxin-1 expression in TNF-α-stimulated fibroblasts by suppressing p38 MAPK-dependent NF-κB signaling. | 2013 Aug |
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Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity. | 2013 Jun |
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Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I. | 2014 Nov |
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Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate. | 2017 |
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Dimethyl fumarate treatment alters NK cell function in multiple sclerosis. | 2018 Feb |
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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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29108094
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.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C718
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MALEIC ACID
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