dimethyl fumarate   Click here for help

GtoPdb Ligand ID: 7045

Synonyms: BG-12 | BG00012 | fumaric acid | Tecfidera®
Approved drug PDB Ligand Immunopharmacology Ligand
dimethyl fumarate is an approved drug (FDA (2013), EMA (2014))
Compound class: Synthetic organic
Comment: The active metabolite of dimethyl fumarate is monomethyl fumarate.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 0
Rotatable bonds 4
Topological polar surface area 52.6
Molecular weight 144.04
XLogP 0.23
No. Lipinski's rules broken 0
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Canonical SMILES COC(=O)C=CC(=O)OC
Isomeric SMILES COC(=O)/C=C/C(=O)OC
InChI InChI=1S/C6H8O4/c1-9-5(7)3-4-6(8)10-2/h3-4H,1-2H3/b4-3+
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Summary of Clinical Use Click here for help
Dimethylf fumarate is an anti-inflammatory drug used to treat patients with relapsing multiple sclerosis. In June 2017 the EMA approved dimethyl fumarate (Skilarence®) as a treatment for plaque psoriasis.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Although the exact mechanism of action of dimethyl fumarate (DMF) is poorly understood, it is believed that the benefits of using this drug are likely to be due to the anti-inflammatory and cytoprotective actions of its active metabolite. This activity is potentially due to inhibition of KEAP1 (Kelch-like ECH-associated protein 1 inhibitor) regulation of Nrf2 signalling of the antioxidant response when cells experience oxidative stress [5]. A study by Kornberg et al. (2018) shows that DMF (and its active metabolite monomethyl fumarate) inactivates the catalytic activity of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and thereby inhibits aerobic glycolysis in activated immune cells (which switch their primary metabolic pathway to aerobic glycolysis upon activation, and become reliant on this source of energy). The authors conclude that it is primarily this action, which mediates a shift from an inflammatory phenotype to a regulatory phenotype, that brings about the anti-inflammatory effects of DMF [3]. Notably DMF's effects on both KEAP1 and GAPDH are attributable to its cysteine succination ability [1,6].
Other inhibitors of glycolysis, such as metformin, and inhibitors of glutamine metabolism are also being examined for anti-inflammatory effects in immune mediated diseases [4,7].
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