Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C4H2O4.2Na |
| Molecular Weight | 160.0358 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].[O-]C(=O)\C=C/C([O-])=O
InChI
InChIKey=MSJMDZAOKORVFC-UAIGNFCESA-L
InChI=1S/C4H4O4.2Na/c5-3(6)1-2-4(7)8;;/h1-2H,(H,5,6)(H,7,8);;/q;2*+1/p-2/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.
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 |
|---|---|---|---|
Target ID: CHEMBL6182 |
|||
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: WP2884 |
|||
Target ID: GO:0070269 |
|||
Target ID: Q16236 Gene ID: 4780.0 Gene Symbol: NFE2L2 Target Organism: Homo sapiens (Human) |
|||
Target ID: Glutathione S-transferase |
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 Date2013 |
|||
| 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 Date2013 |
|||
| 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 |
|
| Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis. | 1986 Mar |
|
| Menstrual migraine and intermittent ergonovine therapy. | 1989 Jun |
|
| Antifungal activity of fumaric acid in mice infected with Candida albicans. | 1991 Nov |
|
| Physiology and pathophysiology of organic acids in cerebrospinal fluid. | 1993 |
|
| [Studies on the mechanisms of renal damages induced by nephrotoxic compounds]. | 1995 Dec |
|
| Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro. | 1996 Dec |
|
| Experience with intraarterial infusion of styrene maleic acid neocarzinostatin (SMANCS)-lipiodol in pancreatic cancer. | 1999 Jul-Aug |
|
| Protein adsorption from flowing solutions on pure and maleic acid copolymer modified glass particles. | 2006 Aug 1 |
|
| Effects of antiglaucoma drugs on collagen gel contraction mediated by human corneal fibroblasts. | 2006 Jun |
|
| The psoriasis drug monomethylfumarate is a potent nicotinic acid receptor agonist. | 2008 Oct 31 |
|
| Molecular mechanisms of Nrf2-mediated antioxidant response. | 2009 Feb |
|
| 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 |
|
| 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 |
|
| Role of Nuclear Factor (Erythroid-Derived 2)-Like 2 Signaling for Effects of Fumaric Acid Esters on Dendritic Cells. | 2017 |
|
| 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 |
|
| Dimethyl fumarate treatment alters NK cell function in multiple sclerosis. | 2018 Feb |
|
| Multiple mechanisms of dimethyl fumarate in amyloid β-induced neurotoxicity in human neuronal cells. | 2018 Feb |
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.
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SUBSTANCE RECORD
