Dimethyl fumarate is an anti-inflammatory. It is indicated for multiple sclerosis patients with relapsing forms and is also being investigated for the treatment of psoriasis. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.
|External IDs||AZL O 211089 / AZL-O-211089 / BG 00012 / BG 12 / BG-00012 / BG-12 / BG00012 / FAG-201 / FP-187 / FP187|
|Product Ingredients||Not Available|
|Approved Prescription Products|
|Approved Generic Prescription Products||Not Available|
|Approved Over the Counter Products||Not Available|
|Unapproved/Other Products||Not Available|
|International Brands||Not Available|
|Brand mixtures||Not Available|
|Weight||Average: 144.1253 |
Used in multiple sclerosis patients with relapsing forms.
The physiological effects dimethyl fumarate has on the body is not well understood. It is known that dimethyl fumarate has anti-inflammatory and cytoprotective effects, which both are likely involved in its actions in multiple sclerosis patients.
|Mechanism of action|
The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF). MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. As well MMF is an agonist at the nicotinic acid receptor, but the relevance of this is not known.
Once ingested, dimethyl fumarate is rapidly hydroylyzed by esterases to MMF. Thus there is negligible amount of dimethyl fumarate in the body, and all pharmacokinetic information is quantified with MMF. In multiple sclerosis patients, the time to maximum concentration of MMF is 2 to 2.5 hours and the maximum concentration is 1.87 mg/L.
|Volume of distribution|
In healthy people, MMF has a variable volume of distribution of 53 to 73 litres.
MMF has a plasma protein binding range of 27 to 45%, and the binding is concentration independent.
Dimethly fumarate is hydrozlied to its metabolite MMF in the GIT, tissues, and blood by esterases. MMF then undergoes subsequent metabolism in the tricarboxylic acid (TCA) cycle. Altogether the main metabolites formed are MMF, glucose, citric acid, and fumaric.
|Route of elimination|
The main route of elimination is by CO2 exhalation that accounts for 60% of the dose. The other minor routes are through the kidney (16% metabolites and trace amounts of unchanged MMF) and the feces (1%).
MMF has a short half life of about 1 hour, and MMF does not accumulate after repeated doses of dimethyl fumarate.
MMF clearance was not quantified.
The most common side effects observed were nausea, diarrhea, abdominal pain, and flushing.
|Pharmacogenomic Effects/ADRs||Not Available|
|Synthesis Reference||Not Available|
|AHFS Codes||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (388 KB)|
|MSDS||Download (355 KB)|
|Predicted ADMET features||Not Available|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of chemical entities known as fatty acid esters. These are carboxylic ester derivatives of a fatty acid.|
|Super Class||Organic compounds|
|Class||Lipids and lipid-like molecules|
|Sub Class||Fatty Acyls|
|Direct Parent||Fatty acid esters|
|Alternative Parents||Dicarboxylic acids and derivatives / Methyl esters / Enoate esters / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds|
|Substituents||Fatty acid ester / Dicarboxylic acid or derivatives / Alpha,beta-unsaturated carboxylic ester / Enoate ester / Methyl ester / Carboxylic acid ester / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative|
|Molecular Framework||Aliphatic acyclic compounds|
|External Descriptors||diester, methyl ester, enoate ester (CHEBI:76004 )|
- Pharmacological action
- General Function:
- Transcription factor binding
- Specific Function:
- Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. ...
- Gene Name:
- Uniprot ID:
- Molecular Weight:
- 69665.765 Da
- Oh CJ, Kim JY, Choi YK, Kim HJ, Jeong JY, Bae KH, Park KG, Lee IK: Dimethylfumarate attenuates renal fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-beta/Smad signaling. PLoS One. 2012;7(10):e45870. doi: 10.1371/journal.pone.0045870. Epub 2012 Oct 8. [PubMed:23056222 ]