Encyclopedia of Cancer

Living Edition
| Editors: Manfred Schwab

Dimethylfumarate

Living reference work entry
DOI: https://doi.org/10.1007/978-3-642-27841-9_1632-2

Definition

Fumaric acid is one of two isomeric unsaturated dicarboxylic acids with the formula HO2CCH=CHCO2H (the other being maleic acid with carboxylic acid groups in cis). Reactions with alcohol create fumaric acid esters (FAE) and water.

Chemistry and Pharmacodynamics

Dimethyl fumarate (DMF) is a lipophilic ester of fumaric acid (Fumaric acid is a dicarbonic acid and a component of the intracellular citric acid cycle). DMF is rapidly hydrolyzed to methyl hydrogen fumarate (MHF) in aqueous solutions at physiological pH.

In both DMF and MHF, nucleophiles can be added to the double bonds in the center of the molecule by a so-called Michaelis-type addition. Thus, they interact with thiols, as given in the tripeptide glutathione (GSH) or with cystein residues in larger proteins. This reactivity of DMF is higher than that of MHF (Fig. 1).

Keywords

Fumaric Acid Psoriasis Patient Dimethyl Fumarate Granuloma Annulare Cutaneous Sarcoidosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Kastrati I, Siklos MI, Calderon-Gierszal EL et al (2016) Dimethyl Fumarate Inhibits the Nuclear Factor κB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein. J Biol Chem. 291(7):3639–47. doi: 10.1074/jbc.M115.679704. Epub 2015 Dec 18
  2. Lehmann J, Listopad J, Rentzsch C et al (2007) Dimethylfumarate induces immunosuppression via glutathione depletion and subsequent induction of heme oxygenase 1. J Invest Dermatol 127:635–645CrossRefGoogle Scholar
  3. Loewe R, Holnthoner W, Gröger M et al (2002) Dimethylfumarate inhibits TNF-induced nuclear entry of NF-κB/p65 in human endothelial cells. J Immunol 168:4781–4787CrossRefPubMedGoogle Scholar
  4. Loewe R, Valero T, Kremling S et al (2006) Dimethylfumarate impairs melanoma growth and metastasis. Cancer Res 66:11888–11896CrossRefPubMedGoogle Scholar
  5. Pereira MA, Barnes LH, Rassman VL et al (1994) Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis 15:1049–1054CrossRefPubMedGoogle Scholar
  6. Schmidt TJ, Ak M, Mrowietz U (2007) Reactivity of dimethyl fumarate and methylhydrogen fumarate towards glutathione and N-acetyl-l-cysteine – preparation of S-substituted thiosuccinic acid esters. Bioorg Med Chem 15:333–342CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Department of Dermatology, Division of General DermatologyMedical University of ViennaViennaAustria