Dimethyl fumarate
Identification
- Summary
Dimethyl fumarate is a medication used to treat patients with the relapsing-remitting form of multiple sclerosis.
- Brand Names
- Tecfidera
- Generic Name
- Dimethyl fumarate
- DrugBank Accession Number
- DB08908
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Dimethyl fumarate (DB08908)
- Weight
- Average: 144.1253
Monoisotopic: 144.042258744 - Chemical Formula
- C6H8O4
- Synonyms
- (E)-But-2-enedioic acid dimethyl ester
- 1,2-bis(methoxycarbonyl)-trans-ethylene
- Dimethyl fumarate
- Dimethyl trans-ethylenedicarboxylate
- Dimethylfumarat
- Fumaric acid, dimethyl ester
- trans-1,2-Ethylenedicarboxylic acid dimethyl ester
- trans-Butenedioic acid dimethyl ester
- External IDs
- AZL O 211089
- AZL-O-211089
- BG 00012
- BG 12
- BG-00012
- BG-12
- BG00012
- FAG-201
- FP-187
- FP187
Pharmacology
- Indication
Used in multiple sclerosis patients with relapsing forms.
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- Contraindications & Blackbox Warnings
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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.
Target Actions Organism AKelch-like ECH-associated protein 1 binderHumans UTranscription factor p65 Not Available Humans - Absorption
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.
- Protein binding
MMF has a plasma protein binding range of 27 to 45%, and the binding is concentration independent.
- Metabolism
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%).
- Half-life
MMF has a short half life of about 1 hour, and MMF does not accumulate after repeated doses of dimethyl fumarate.
- Clearance
MMF clearance was not quantified.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The most common side effects observed were nausea, diarrhea, abdominal pain, and flushing.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Dimethyl fumarate. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Dimethyl fumarate. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Dimethyl fumarate. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Dimethyl fumarate. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Dimethyl fumarate. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Dimethyl fumarate. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Dimethyl fumarate. Altretamine The risk or severity of adverse effects can be increased when Altretamine is combined with Dimethyl fumarate. Amsacrine The risk or severity of adverse effects can be increased when Amsacrine is combined with Dimethyl fumarate. Anakinra The risk or severity of adverse effects can be increased when Anakinra is combined with Dimethyl fumarate. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Take with food. Co-administration with food may reduce gastrointestinal upset and flushing.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Monomethyl fumarate unknown 45IUB1PX8R 2756-87-8 NKHAVTQWNUWKEO-NSCUHMNNSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dimethyl Fumarate Capsule 240 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2020-09-28 Not applicable US 
Dimethyl Fumarate Capsule 120 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2020-09-28 Not applicable US Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU 
Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 30 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 30 mg Oral Almirall S.A 2020-12-16 Not applicable EU Skilarence Tablet, delayed release 120 mg Oral Almirall S.A 2020-12-16 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Dimethyl Fumarate Capsule, delayed release 120 mg/1 Oral Zydus Pharmaceuticals (USA) Inc. 2020-09-28 Not applicable US Dimethyl Fumarate Capsule, delayed release 240 mg/1 Oral Amneal Pharmaceuticals NY LLC 2020-09-28 Not applicable US Dimethyl Fumarate Capsule 120 mg/1 Oral Glenmark Pharmaceuticals Inc., USA 2020-10-06 Not applicable US Dimethyl Fumarate Capsule, delayed release 120 mg/1 Oral TWi Pharmaceuticals, Inc. 2020-12-01 Not applicable US Dimethyl fumarate Capsule, delayed release 240 mg/1 Oral Mylan Pharmaceuticals Inc. 2020-08-18 Not applicable US Dimethyl Fumarate Capsule, delayed release 240 mg/1 Oral Cipla USA Inc. 2020-09-24 Not applicable US Dimethyl fumarate Capsule, delayed release 120 mg/1 Oral Ascend Laboratories, LLC 2020-09-26 Not applicable US Dimethyl fumarate Capsule 240 mg/1 Oral PHARMATHEN INTERNATIONAL S.A. 2021-08-01 Not applicable US Dimethyl Fumarate Capsule, delayed release 240 mg/1 Oral Dr. Reddy's Laboratories Inc. 2020-09-28 Not applicable US Dimethyl Fumarate Capsule, delayed release 240 mg/1 Oral Msn Laboratories Private Limited 2020-09-28 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Ascend Laboratories, LLC 2020-09-26 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Camber Pharmaceuticals, Inc. 2020-09-24 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral TWi Pharmaceuticals, Inc. 2020-12-01 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral PHARMATHEN INTERNATIONAL S.A. 2021-08-01 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Cadila Healthcare Limited 2020-09-28 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Amneal Pharmaceuticals NY LLC 2020-09-28 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Glenmark Pharmaceuticals Inc., USA 2020-10-06 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Cipla USA Inc. 2020-09-24 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Msn Laboratories Private Limited 2021-05-20 Not applicable US Dimethyl Fumarate Dimethyl fumarate (120 mg/1) + Dimethyl fumarate (240 mg/1) Oral Zydus Pharmaceuticals (USA) Inc. 2020-09-28 Not applicable US
Categories
- ATC Codes
- L04AX07 — Dimethyl fumarate
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as fatty acid esters. These are carboxylic ester derivatives of a fatty acid.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Fatty Acyls
- Sub Class
- Fatty acid esters
- Direct Parent
- Fatty acid esters
- Alternative Parents
- Dicarboxylic acids and derivatives / Methyl esters / Enoate esters / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Aliphatic acyclic compound / Alpha,beta-unsaturated carboxylic ester / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Dicarboxylic acid or derivatives / Enoate ester / Fatty acid ester / Hydrocarbon derivative / Methyl ester
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- diester, methyl ester, enoate ester (CHEBI:76004)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- FO2303MNI2
- CAS number
- 624-49-7
- InChI Key
- LDCRTTXIJACKKU-ONEGZZNKSA-N
- InChI
- InChI=1S/C6H8O4/c1-9-5(7)3-4-6(8)10-2/h3-4H,1-2H3/b4-3+
- IUPAC Name
- 1,4-dimethyl (2E)-but-2-enedioate
- SMILES
- [H]\C(=C(\[H])C(=O)OC)C(=O)OC
References
- General References
- Papadopoulou A, D'Souza M, Kappos L, Yaldizli O: Dimethyl fumarate for multiple sclerosis. Expert Opin Investig Drugs. 2010 Dec;19(12):1603-12. doi: 10.1517/13543784.2010.534778. Epub 2010 Nov 11. [Article]
- External Links
- KEGG Drug
- D03846
- PubChem Compound
- 637568
- PubChem Substance
- 347827812
- ChemSpider
- 553171
- 1373478
- ChEBI
- 76004
- ChEMBL
- CHEMBL2107333
- ZINC
- ZINC000003843378
- PharmGKB
- PA166152838
- PDBe Ligand
- EOU
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dimethyl_fumarate
- PDB Entries
- 6lrz
- FDA label
- Download (388 KB)
- MSDS
- Download (355 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Psoriasis Vulgaris (Plaque Psoriasis) 1 4 Completed Basic Science Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Completed Other Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Completed Treatment Multiple Sclerosis 3 4 Completed Treatment Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis 1 4 Completed Treatment Multiple Sclerosis / Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Completed Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 2 4 Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 4 Terminated Health Services Research Multiple Sclerosis 1 4 Terminated Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule, delayed release Oral Capsule, delayed release Oral 120 mg/1 Capsule, delayed release Oral 240 mg/1 Tablet Oral 120 MG Tablet Oral 30 MG Tablet, delayed release Oral 120 mg Tablet, delayed release Oral 30 mg Tablet, extended release Oral 30 MG Capsule, delayed release Oral 120 mg Capsule, delayed release Oral 240 mg Capsule Oral 120 mg/1 Capsule Oral 240 mg/1 Capsule Oral Solution Oral 120.0 mg Solution Oral 240.0 mg Capsule, coated Oral 120 mg Capsule, coated Oral 240 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7320999 No 2008-01-22 2020-05-18 US US7619001 No 2009-11-17 2018-04-01 US US7803840 No 2010-09-28 2018-04-01 US US8399514 No 2013-03-19 2028-02-07 US US8524773 No 2013-09-03 2018-04-01 US US6509376 No 2003-01-21 2019-10-29 US US8759393 No 2014-06-24 2019-10-29 US US10391160 No 2019-08-27 2035-03-13 US US10959972 No 2021-03-30 2035-11-16 US US10555993 No 2020-02-11 2035-03-13 US US10994003 No 2015-03-13 2035-03-13 US US11007166 No 2015-11-16 2035-11-16 US US11007167 No 2015-11-16 2035-11-16 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 103 to 104 From MSDS. boiling point (°C) 192 to 193 From MSDS. water solubility Highly soluble in water. From FDA label. - Predicted Properties
Property Value Source Water Solubility 12.9 mg/mL ALOGPS logP 0.45 ALOGPS logP 0.72 ChemAxon logS -1 ALOGPS pKa (Strongest Basic) -6.5 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 2 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 52.6 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 34.15 m3·mol-1 ChemAxon Polarizability 13.76 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- 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 s...
- Gene Name
- KEAP1
- Uniprot ID
- Q14145
- Uniprot Name
- Kelch-like ECH-associated protein 1
- Molecular Weight
- 69665.765 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Target undergoes covalent modification involving the cysteine 38 residue. This prevents nuclear translocation of the protein.
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related...
- Gene Name
- RELA
- Uniprot ID
- Q04206
- Uniprot Name
- Transcription factor p65
- Molecular Weight
- 60218.53 Da
References
- Kastrati I, Siklos MI, Calderon-Gierszal EL, El-Shennawy L, Georgieva G, Thayer EN, Thatcher GR, Frasor J: Dimethyl Fumarate Inhibits the Nuclear Factor kappaB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein. J Biol Chem. 2016 Feb 12;291(7):3639-47. doi: 10.1074/jbc.M115.679704. Epub 2015 Dec 18. [Article]
Drug created on June 20, 2013 01:12 / Updated on October 22, 2021 23:18