Dimethyl Fumarate: An Anti Psoriasis Drug Works Against Tumors


A recent press release from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) discuss the results of German researchers who demonstrated that dimethyl fumarate (DMF), a drug used to treat Psoriasis patients can also help in the fight against cancer. This study has been performed on lymphomas and DMF appears to have at least comparable effectiveness and is better tolerated than most other substances that are used to treat cutaneous lymphomas. It has been shown that DMF  selectively kills tumor cells, leaving healthy T cells unaffected. Following this finding, the investigators have already initiated a clinical trial (Ref.)

FumariaDimethyl fumarate (DMF) belongs to a class of molecules known as fumaric acid esters (FAEs), a known component of a centuries-old herbal medicine. Indeed, esters of fumarate are found in the leaves of the herb Fumaria officinalis, which is an herbal remedy recognized for its historical use as a diuretic, and as a remedy for eczema, asthma, and gastrointestinal disorders. Due to its historical use as an herbal remedy, in the 1950s, a chemist in Germany (Schweckendiek) isolated fumaric acid from the plant and tested its efficacy in the treatment of psoriasis.

DMF has been an approved drug in Europe for several decades as a therapeutic for psoriasis and relapsing-remitting multiple sclerosis (MS). Might be also useful for treating, asthma, aggressive breast cancers, hematopoeitic tumors, inflammatory bowel disease, intracerebral hemorrhage, osteoarthritis, chronic pancreatitis, and retinal ischemia. (Ref.)

While this is just the article that triggered my attention, I now found out that there is much more research previously performed indicating the potential role of DMF in the battle against cancer.

Indeed. previously it has been shown that DMF is also effective against:

  • breast cancer (Ref.)
    • These results establish DMF as an NFκB inhibitor with anti-tumor activity that may add therapeutic value in the treatment of aggressive breast cancers.
  • cervical cancer cells (Ref.)
  • cutaneous T-cell lymphoma (Ref.)
    • DMF treatment is of particular promise in CTCL because DMF is already in successful clinical use in the treatment of psoriasis and multiple sclerosis allowing fast translation into clinical studies in CTCL.
  • brain, breast, lung and ovarian cancer cells (Ref.)
  • hematopoietic tumor cell (Ref.)
  • colon cancer (Ref.)
  • glioblastomas (Ref.)
    • DMF appears to have a promising role in the treatment of malignant brain neoplasms. DMF reduced proliferation rate, generated cell lysis, decreased the expression of NF-κB, and restricted the growth of CD133 cells in gliomas. This suggests that DMF may be considered for further antitumor studies, and provide a new treatment modality for brain tumors.
  • melanoma (Ref.)

DMF is a (new) antilymphangiogenic compound and might be used in various illnesses associated with increased lymphangiogenesis, such as lymphoedema, cancer or psoriasis, which are associated with abnormal lymphatic vessel formation (Ref.)

DMF has also been proposed to be repurposed as a therapeutic strategy to reinforce endogenous brain defense mechanisms against Parkinson’s disease (PD) – associated synucleinopathy.

As a result of its potential, it has been proposed to reproposed DMF as an anti-cancer drug (Ref.)

Note, that a good part of the research published on DMF has been published very recently, i.e. 2016.

I specifically like this statement from the Department of Dermatology, Venereology and Allergology, University of Frankfurt, Germany: “Fumaric acid esters have been used successfully in the therapy of psoriasis vulgaris since 1959. In the last 17 years, many of the underlying mechanisms of anti-psoriatic action, such as a Th1/Th2 shift, a suppression of important leukocyte adhesion molecules, the induction of pro-apoptotic pathways in T-cells and recently anti-angiogenic action, have been discovered. Based on the knowledge of these immunomodulatory characteristics, fumaric acid esters have been shown to be effective or potentially effective in a multitude of dermatological as well as non-dermatological diseases. The range of new therapeutic targets reaches from multiple sclerosis to illnesses such as necrobiosis lipoidica, granuloma annulare and sarcoidosis. Experimental approaches offer promising, although preliminary, results on the treatment of cancer, malaria, chronic inflammatory lung diseases, and Huntington disease, to name but a few. This valued and well-known drug mainly prescribed by dermatologists is now experiencing a renaissance far beyond dermatologic applications.” (Ref.)

Anti Cancer Mechanisms:

One of the major mechanism through which DMF acts against cancer is connected to Nrf2.

However, strangely enough DMF activates Nrf2 by “inhibiting its inhibitor” (Ref.). But due to reasons discussed below we want to deactivate Nrf2 which is what DMF can also do.

Inhibiting the inhibitor of Nrf2, leads to the activation of Nrf2 and promotes gene expression of detoxification enzymes such as glutathione S-transferase A2 (GSTA2), hemoxygenase, and NADPH quinone oxidoreductase 1 (NQO1) indicating that DMF also exhibits antioxidant activity.

Due to this antioxidant character, the Nrf2  activation is actually known to protect cancer cells as well as enhances cancer cell proliferation and promotes chemoresistance in several cancers. This is strange given that DMF has been shown to kill multiple types of cancer cells.

However, this “paradox” has been recently explained: “We demonstrated that at lower concentrations (< 25 mM), DMF has a cytoprotective role through activation of the NRF2 antioxidant pathway. At higher concentrations, however (> 25 mM), DMF caused oxidative stress and subsequently cytotoxicity in several cancer cell lines. High DMF concentration decreases nuclear translocation of NRF2 and production of its downstream targets. The pro-oxidative and cytotoxic effects of high concentration of DMF were abrogated by over-expression of NRF2 in OVCAR3 cells, suggesting that DMF cytotoxicity is dependent of NRF2 depletion.” (Ref.)

So one of the main anti cancer mechanism of DMF is connected with a decrease of the nuclear translocation of NRF2 and that should happen when higher dose of DMF is administrated.

The relevance of NRF2 as a redox master regulation, on pancreatic cancer for example, has been very recently discussed in the following Nature Review paper http://www.nature.com/nrgastro/journal/v13/n9/full/nrgastro.2016.133.html

Other Nrf2 inhibitors are: Flavonoids (Luteolin, apigenin and chrysin, Wogonin, 4-Methoxychalcone, 3′,4′,5′,5,7-Pentamethoxyflavone, Epigalocatechin 3-gallate, Isoniazid, Ethionamide), Vitamins and their derivatives (Ascorbic acid, Retinoic acid), Others (Brusatol, Cryptotanshinone, Metformin, Ochratoxin A, Trigonelline, Triptolide). The potential target sites and mechanisms of various Nrf2-inhibitors is shown in the picture below (Ref.)

Source of the figure above: (Ref.)

DMF has multiple roles through which helps fighting cancer:

  • DMF effectively blocks NFκB activity (Ref.1, Ref.2, Ref.3)
    • Activation of transcription factor NF-kappaB is frequently encountered in tumor cells and contributes to aggressive tumor growth and resistance to chemotherapy and ionizing radiation during cancer treatment. Accumulating evidence over the last few years indicate that most chemotherapeutic agents and radiation therapy activate NF-kappaB in vitro and in vivo. Moreover, induction of chemoresistance and radioresistance is mediated through several genes regulated by NF-kappaB and inhibition of this transcription factor increases sensitivity of cancer cells to the apoptotic action of chemotherapeutic agents and to radiation exposure. (Ref.)
  • Decrease of the nuclear translocation of NRF2. (NRF2 is a transcription factor that moves into the nucleus of cells and stimulates production of the antioxidant glutathione in cells.) This leads to the depletion of intracellular Glutathione (GSH) (Ref.) that was also connected to the G6PDH and GR inhibition (Ref.)
    • via these inhibitory effects on the lipogenic enzyme G6PDH and GR activities and their potential to deplete GSH, Dimethyl fumarate might cause a moderate and, if necessary, strong systemic decrease in the NADPH and GSH production, depending on the concentration used (Ref.)
  • p21 expression modulation (Ref.)
  • anti metastasis (Ref.)

However, other mechanisms have also been associated with DMF, which include effects on monocytes, dendritic cells, T cells, and natural killer cells. (Ref.1, Ref.2). On this line, some of the mechanisms may be very relevant but they could also antagonize the anti cancer effects of other drugs such as Plerixafor due to the following mechanisms

  • DMF treatment inhibited proliferation and production of Th1 cytokines by human blood lymphocytes (Ref.)
  • DMF treatment of experimental autoimmune encephalomyelitis (EAE) was also associated with a Th2 bias, which may be a consequence of induction of antigen-presenting antiinflammatory type II dendritic cells (DCs) (Ref.1, Ref.2)
  • The clinical benefit of DMF treatment in both Nrf2−/−and WT mice was associated with a reduction of Th1 and Th17 cells as well as the induction of antiinflammatory M2 monocytes (proinflammatory T-cell subsets, include Th1, Th17, and GM-CSF–producing T cells) (Ref.)

Dose and Administration:

For multiple sclerosis, drug label indicates the starting dose for TECFIDERA is 120 mg twice a day orally. After 7 days, the dose should be increased to the maintenance dose of 240 mg twice a day orally. (Ref.)

For cancer, the effective dose it is not yet known but at least the above is a good reference point for a safe dose.

Due to high doses that are given orally (120 to 240 mg DMF per tablet) high local concentrations can be assumed after release in the gut lumen. Due to high lipophilicity DMF can penetrate into the mucosa and may affect immune cells and red blood cells in the local vasculature. Unfortunately, there is no published literature about local DMF concentration in the small intestine neither in animals nor in man. (Ref.)

Safety Profile:

According to SUMMARY OF PRODUCT CHARACTERISTICS (Ref.) the safety profile of Tecfidera includes the following:

The most common adverse reactions (incidence ≥10%) for patients treated with Tecfidera were flushing and gastrointestinal events (i.e. diarrhoea, nausea, abdominal pain, abdominal pain upper). Flushing and gastrointestinal events tend to begin early in the course of treatment (primarily during the first month) and in patients who experience flushing and gastrointestinal events, these events may continue to occur intermittently throughout treatment with Tecfidera. The most commonly reported adverse reactions leading to discontinuation (incidence >1%) in patients treated with Tecfidera were flushing (3%) and gastrointestinal events (4%). (Ref.)

An anecdotal report on DMF safety profile: http://www.dmfms.de/dmf_e.htm



Fumaderm (a combination drug composed of DMF and monoethyl fumarate (MEF) salts) is registered for treatment of moderate-to-severe psoriasis since 1984 in Germany, while in recent years, Tecfidera was approved in EU and US for treatment of multiple sclerosis.

Tecfidera can be very expensive, at about 50.000 euro/year. However, here is an example of how when self made it can become as cheap as about 100 euro/month: http://www.dmfms.de/dmf_e.htm [website of Jürgen Erhardt (Dr. rer. nat.)].

CAS #: 624-49-7

Other references:

Repurposing Tecfidera for cancerhttp://www.ncbi.nlm.nih.gov/pubmed/27429364

Mechanisms of drug action: the potential of dimethylfumarate for the treatment of neoplasms. http://www.ncbi.nlm.nih.gov/pubmed/21566574

Recent advances in the biomedical applications of fumaric acid and its ester derivatives: The multifaceted alternative therapeutics. http://www.ncbi.nlm.nih.gov/pubmed/26922546

Several lines of evidence have demonstrated the potential biomedical applications of fumaric acid (FA) and its ester derivatives against many human disease conditions. Fumaric acid esters (FAEs) have been licensed for the systemic treatment of the immune-mediated disease psoriasis. Biogen Idec Inc. announced about the safety and efficacy of the formulation FAE (BG-12) for treating RRMS (relapsing-remitting multiple sclerosis). Another FAE formulation DMF (dimethyl fumarate) was found to be capable of reduction in inflammatory cardiac conditions, such as autoimmune myocarditis and ischemia and reperfusion. DMF has also been reported to be effective as a potential neuroprotectant against the HIV-associated neurocognitive disorders (HAND). Many in vivo studies carried out on rat and mice models indicated inhibitory effects of fumaric acid on carcinogenesis of different origins. Moreover, FAEs has emerged as an important matrix ingredient in the fabrication of biodegradable scaffolds for tissue engineering applications. Drug delivery vehicles composed of FAEs have shown promising results in delivering some leading drug molecules. Apart from these specific applications and findings, many more studies on FAEs have revealed new therapeutic potentials with the scope of clinical applications. However, until now, this scattered vital information has not been written into a collective account and analyzed for minute details. The aim of this paper is to review the advancement made in the biomedical application of FA and FAEs and to focus on the clinical investigation and molecular interpretation of the beneficial effects of FA and FAEs.

DMF, but not other fumarates, inhibits NF-κB activity in vitro in an Nrf2-independent manner. http://www.ncbi.nlm.nih.gov/pubmed/26004161

Fumarate-containing pharmaceuticals are potent therapeutic agents that influence multiple cellular pathways. Despite proven clinical efficacy, there is a significant lack of data that directly defines the molecular mechanisms of action of related, yet distinct fumarate compounds. We systematically compared the impact of dimethyl fumarate (DMF), monomethyl fumarate (MMF) and a mixture of monoethyl fumarate salts (Ca(++), Mg(++), Zn(++); MEF) on defined cellular responses. We demonstrate that DMF inhibited NF-κB-driven cytokine production and nuclear translocation of p65 and p52 in an Nrf2-independent manner. Equivalent doses of MMF and MEF did not affect NF-κB signaling. These results highlight a key difference in the biological impact of related, yet distinct fumarate compounds.

Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2. http://www.ncbi.nlm.nih.gov/pubmed/27078105

Dimethyl fumarate (DMF) (BG-12, Tecfidera) is a fumaric acid ester (FAE) that was advanced as a multiple sclerosis (MS) therapy largely for potential neuroprotection as it was recognized that FAEs are capable of activating the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, DMF treatment in randomized controlled MS trials was associated with marked reductions in relapse rate and development of active brain MRI lesions, measures considered to reflect CNS inflammation. Here, we investigated the antiinflammatory contribution of Nrf2 in DMF treatment of the MS model, experimental autoimmune encephalomyelitis (EAE). C57BL/6 wild-type (WT) and Nrf2-deficient (Nrf2(-/-)) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (p35-55) for EAE induction and treated with oral DMF or vehicle daily. DMF protected WT and Nrf2(-/-) mice equally well from development of clinical and histologic EAE. The beneficial effect of DMF treatment in Nrf2(-/-) and WT mice was accompanied by reduced frequencies of IFN-γ and IL-17-producing CD4(+) cells and induction of antiinflammatory M2 (type II) monocytes. DMF also modulated B-cell MHC II expression and reduced the incidence of clinical disease in a B-cell-dependent model of spontaneous CNS autoimmunity. Our observations that oral DMF treatment promoted immune modulation and provided equal clinical benefit in acute EAE in Nrf2(-/-) and WT mice, suggest that the antiinflammatory activity of DMF in treatment of MS patients may occur through alternative pathways, independent of Nrf2.


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11 thoughts on “Dimethyl Fumarate: An Anti Psoriasis Drug Works Against Tumors

  1. We stopped because nobody bought it anymore. There was just one German prescriber.
    No problems with quality, efficacy or safety. So we are happy to start compounding again, if you have enough people who want it!

  2. Hi Daniel,

    You can get the raw chemical much cheaper. I recently air freighted 25 kg of 98% DMF from China for $620 US (total cost), enough for 300 treatment years. For £343 UK (excluding postage and handling) I could have bought 14*120 mg tablets of Tecfidera, which would last me for a week and equates to less than 4.2 cents US worth of the raw stuff I bought. I have been taking the raw chemical since December 2012. It has provided excellent control of my psoriasis, psoriatic arthropathy and ankylosing spondylitis. My use is experimental. I take 2*810 mg weekly which is at variance to the standard dosing regime. I am currently testing a micronised DMF.

    1. Thanks a lot Bill for the info! Indeed, I also used to order various substances from China, for own needs. The challenge was to find suppliers that I could trust, but once I found them, many things have become accessible.

  3. @Daniel: can you confirm or not what is written in Wiki, about DMF being an allergic sensitizer?
    While searching for new treatments against Kras-mutant cancers, I found this interesting article, but it requires high concentrations of DMF:
    Dimethyl fumarate is highly cytotoxic in KRAS mutated cancer cells but spares non-tumorigenic cells. PMID: 29507676

    1. In very low concentrations, DMF is a potent sensitizer that can cause severe allergic contact dermatitis…
      Dimethylfumarate (DMF) was the cause of a major outbreak of allergic contact dermatitis as a consequence of its use as an antifungal agent in leather products, particularly in furniture, with what became known as ‘toxic sofa dermatitis’.

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