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Dimethyl fumarate | CAS No: 624-49-7 | GMP-certified suppliers
A medication that treats relapsing forms of multiple sclerosis by providing immunomodulatory and anti-inflammatory benefits to reduce disease progression and relapse frequency in adults.
Therapeutic categories
Primary indications
- Dimethyl fumarate is indicated for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
Product Snapshot
- Dimethyl fumarate is formulated primarily as oral capsules and tablets with various release profiles including delayed and extended release
- It is mainly used in the treatment of relapsing forms of multiple sclerosis in adult patients
- The product is approved for use in key regulatory markets including the US, Canada, and the European Union
Clinical Overview
The precise mechanism of action of dimethyl fumarate in MS remains incompletely characterized. It is metabolized in vivo to monomethyl fumarate (MMF), its active metabolite. Both dimethyl fumarate and MMF modulate cellular pathways by up-regulating the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway, a key regulator of oxidative stress response. Additionally, these compounds exhibit anti-inflammatory effects partly through suppression of pro-inflammatory gene expression mediated via nuclear factor kappa B inhibition. MMF also acts as an agonist at the nicotinic acid receptor; however, the clinical relevance of this interaction is not well established. Immunomodulatory actions include altering lymphocyte subsets and reducing central nervous system infiltration by pro-inflammatory T cell populations, contributing to a shift towards an anti-inflammatory immune milieu.
Pharmacodynamically, dimethyl fumarate exhibits cytoprotective and anti-inflammatory properties. It does not significantly prolong cardiac QT intervals. Pharmacokinetic data indicate rapid metabolism to MMF; however, detailed ADME parameters vary and are influenced by first-pass metabolism.
Safety considerations encompass risks of lymphopenia, liver injury, serious opportunistic infections including cases of progressive multifocal leukoencephalopathy, and hypersensitivity reactions such as anaphylaxis and angioedema. Monitoring for hematologic and hepatic adverse events is recommended during treatment.
Dimethyl fumarate was first used in psoriasis treatment in Germany before its regulatory approval as a disease-modifying therapy for MS by the FDA, where it was the third oral agent approved in this class.
For pharmaceutical development and sourcing, emphasis on high-purity raw material is critical due to the compound’s susceptibility to hydrolysis and oxidative degradation. Consistent manufacturing controls and robust impurity profiling align with global regulatory expectations to ensure API quality and performance in formulation.
Identification & chemistry
| Generic name | Dimethyl fumarate |
|---|---|
| Molecule type | Small molecule |
| CAS | 624-49-7 |
| UNII | FO2303MNI2 |
| DrugBank ID | DB08908 |
Pharmacology
| Summary | Dimethyl fumarate is an immunomodulatory agent indicated for relapsing forms of multiple sclerosis. Its active metabolite, monomethyl fumarate, upregulates the Nrf2 pathway, enhancing cellular response to oxidative stress, and inhibits NF-κB signaling, resulting in reduced pro-inflammatory gene expression. The drug also modulates immune cell phenotype and CNS lymphocyte infiltration, promoting an anti-inflammatory environment. |
|---|---|
| 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). Both dimethyl fumarate and MMF up-regulate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate also suppresses pro-inflammatory genes through nuclear factor kappa B inhibition. Additionally, MMF acts as an agonist at the nicotinic acid receptor, but the relevance of this is unknown. It has been suggested that dimethyl fumarate exerts its immunomodulatory effects through changes in the composition and phenotype of immune cells. It reduces CNS infiltration and alters the composition of all lymphocyte subpopulations, especially for cytotoxic and effector T cells. This causes a shift from a mainly pro-inflammatory phenotype to an anti-inflammatory one. |
| Pharmacodynamics | The physiological effects of dimethyl fumarate on the body are not well understood. It has anti-inflammatory and cytoprotective effects, likely involved in its actions in multiple sclerosis (MS) patients. Dimethyl fumarate does not cause clinically significant QT interval prolongation. However, cases of progressive multifocal leukoencephalopathy, serious opportunistic infections, lymphopenia and liver injury have been reported in MS patients treated with this drug. Dimethyl fumarate may also cause anaphylaxis and angioedema. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Kelch-like ECH-associated protein 1 | Humans | binder |
| Transcription factor p65 | Humans | inhibitor, binder |
ADME / PK
| Absorption | Once ingested, dimethyl fumarate is rapidly hydrolyzed by esterases to form monomethyl fumarate (MMF). Therefore, there is a negligible amount of dimethyl fumarate in the body, and all pharmacokinetic information is quantified with MMF. The time to maximum concentration (t<sub>max</sub>) of MMF ranges between 2 and 2.5 hours. In patients with multiple sclerosis given 240 mg of dimethyl fumarate two times a day with food, the C<sub>max</sub> and AUC were 1.87 mg/L and 8.21 mg⋅hr/L, respectively. High-fat, high-calorie meals decrease the C<sub>max</sub> of MMF by 40% and cause a t<sub>max</sub> delay from 2 hours to 5.5 hours; however, these changes are not considered clinically significant. |
|---|---|
| Half-life | The dimethyl fumarate metabolite monomethyl fumarate (MMF) has a short half-life of about 1 hour. MMF does not accumulate after repeated doses of dimethyl fumarate. |
| Protein binding | Monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate, has a plasma protein binding range of 27 to 45%, and the binding process is concentration-independent. |
| Metabolism | Dimethyl fumarate is quickly hydrolyzed by esterases in the gastrointestinal tract, tissues, and blood to form monomethyl fumarate (MMF), its active metabolite. MMF then undergoes subsequent metabolism through the tricarboxylic acid (TCA) cycle. The main metabolites of dimethyl fumarate are MMF, glucose, citric, and fumaric acid. Cytochrome P450 (CYP) enzymes do not participate in the metabolism of dimethyl fumarate. |
| Route of elimination | The main route of elimination of dimethyl fumarate is by CO<sub>2</sub> exhalation, which accounts for 60% of the dose. The other minor routes of elimination are through the kidney (16% of the dose) and feces (1% of the dose). Trace amounts of unchanged monomethyl fumarate (the active metabolite of dimethyl fumarate) are present in urine. |
| Volume of distribution | In healthy people, monomethyl fumarate (MMF) has a variable volume of distribution of 53 to 73 litres. |
| Clearance | Monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate, has a rapid clearance. Its apparent clearance (Cl/F) appears to be dose-independent. |
Formulation & handling
- Dimethyl fumarate is a small molecule administered exclusively via oral formulations including delayed-release capsules and film-coated tablets.
- It exhibits moderate water solubility and low lipophilicity (LogP 0.72), supporting oral absorption but necessitating formulation strategies for stability and controlled release.
- Administration may be with or without food, though food co-administration can reduce flushing incidence; no strict food sensitivity noted.
Regulatory status
| Lifecycle | The API is marketed in Canada, the US, and the EU, with key patents in the United States expiring between 2018 and 2028, indicating a variable stage of market exclusivity and increasing availability of generic alternatives. |
|---|
| Markets | Canada, US, EU |
|---|
Supply Chain
| Supply chain summary | The manufacturing and supply landscape for dimethyl fumarate includes multiple originator companies marketing branded products predominantly in the US, EU, and Canadian markets. Several patents related to dimethyl fumarate remain active in the US, with the latest expiry date extending to 2028, indicating that generic competition is either limited or expected to increase closer to that time. This suggests a controlled supply environment with ongoing patent protection influencing market entry. |
|---|
Safety
| Toxicity | Cases of overdose with dimethyl fumarate have been reported, and symptoms were consistent with its adverse event profile. There are no known therapeutic interventions to enhance dimethyl fumarate elimination nor an antidote. The product label of dimethyl fumarate recommends initiating symptomatic supportive treatment as clinically indicated in case of overdose. _In vivo_ carcinogenicity studies found that at doses ranging between 200 and 400 mg/kg/day, mice had a higher incidence of non-glandular stomach and kidney tumors. The highest dose not associated with tumors in mice (75 mg/kg/day) is equivalent to the recommended human dose (RHD) of 480 mg/day. Dimethyl fumarate did not show evidence of mutagenicity in the _in vitro_ bacterial reverse mutation (Ames) assay. Dimethyl fumarate was clastogenic in the _in vitro_ chromosomal aberration assay in human peripheral blood lymphocytes in the absence of metabolic activation, but not clastogenic in the _in vivo_ micronucleus assay in the rat. |
|---|
- Overdose cases of dimethyl fumarate have been reported
- No specific antidote or elimination-enhancing treatment is available
- Carcinogenicity observed in mice at high doses (200–400 mg/kg/day) with tumor incidence in stomach and kidneys
Dimethyl fumarate is a type of Immunosuppressants
Immunosuppressants are a vital subcategory of pharmaceutical active pharmaceutical ingredients (APIs) that play a crucial role in medical treatments. These substances are designed to suppress or weaken the immune system's response, making them invaluable in various therapeutic applications.
Immunosuppressants find extensive use in the management of autoimmune diseases, organ transplantation, and the prevention of rejection reactions. By modulating the immune system's activity, these APIs help control excessive immune responses that can lead to tissue damage and chronic inflammation.
There are different classes of immunosuppressants, including corticosteroids, calcineurin inhibitors, antimetabolites, and biologics. Each class targets specific immune pathways to achieve the desired therapeutic effect. Corticosteroids, for instance, are known for their potent anti-inflammatory properties, making them effective in managing conditions such as rheumatoid arthritis and asthma.
Calcineurin inhibitors like cyclosporine and tacrolimus act by inhibiting the activity of calcineurin, a protein involved in immune cell activation. These drugs are commonly used in organ transplantation to prevent the immune system from attacking the transplanted organ.
Antimetabolites interfere with DNA synthesis and cell proliferation, thereby dampening immune responses. They are often prescribed for conditions like psoriasis and rheumatoid arthritis.
Biologic immunosuppressants, such as monoclonal antibodies, target specific immune cells or molecules involved in the disease process. They have revolutionized the treatment of autoimmune diseases like rheumatoid arthritis, Crohn's disease, and psoriasis.
Immunosuppressants require careful administration and monitoring due to their potential side effects and interactions with other medications. Close collaboration between healthcare professionals, pharmacists, and patients is essential to ensure the safe and effective use of these APIs in various therapeutic settings.
Overall, immunosuppressants represent a critical category of pharmaceutical APIs that significantly contribute to improving patients' quality of life by controlling the immune system's activity and managing various autoimmune conditions and transplantation outcomes.
Dimethyl fumarate (Immunosuppressants), classified under Immunomodulators
Immunomodulators, a category of pharmaceutical active pharmaceutical ingredients (APIs), are substances that help regulate and modify the immune response of an individual. These compounds play a crucial role in treating various immune-related disorders and diseases. Immunomodulators work by either enhancing or suppressing the immune system, depending on the specific condition being treated.
Immunomodulators are used in the treatment of autoimmune disorders, such as rheumatoid arthritis, multiple sclerosis, and psoriasis. By suppressing the immune system, these APIs help reduce the overactive immune response associated with these conditions, thereby alleviating symptoms and preventing further damage to the body's tissues.
On the other hand, immunomodulators are also employed to boost the immune system in cases of immunodeficiency disorders. These APIs stimulate the immune response, enabling the body to better fight off infections and diseases. Additionally, immunomodulators are utilized in the prevention and treatment of organ transplant rejection, where they help modulate the immune system to accept the transplanted organ.
The development and production of immunomodulators require rigorous testing and quality control to ensure their safety and efficacy. Pharmaceutical companies carefully formulate these APIs into various dosage forms, including tablets, capsules, injections, and topical preparations, to cater to different patient needs.
In summary, immunomodulators form a vital category of pharmaceutical APIs that regulate and modify the immune system. With their ability to modulate immune responses, these compounds contribute significantly to the management and treatment of various immune-related disorders and diseases, improving the quality of life for many patients.
Dimethyl fumarate API manufacturers & distributors
Compare qualified Dimethyl fumarate API suppliers worldwide. We currently have 25 companies offering Dimethyl fumarate API, with manufacturing taking place in 8 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| ACE Japan | Producer | Japan | Japan | CoA | 76 products |
| Alkem Labs. | Producer | India | India | CoA, USDMF | 22 products |
| Arevipharma | Producer | Germany | Unknown | CoA, USDMF | 25 products |
| Biophore India | Producer | India | India | CoA, USDMF | 46 products |
| Chinoin | Producer | Hungary | Hungary | CoA, GMP | 21 products |
| Dr. Reddy's | Producer | India | India | BSE/TSE, CoA, EDMF/ASMF, FDA, GMP, MSDS, USDMF, WC | 170 products |
| Global Pharma Tek | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, ISO9001, MSDS | 484 products |
| Honour Lab | Producer | India | India | CoA, GMP, USDMF, WC | 30 products |
| Intas Pharma | Producer | United Kingdom | Unknown | CoA, USDMF | 30 products |
| Laboratorium Ofichem B.V. | Producer | Netherlands | Netherlands | BSE/TSE, CoA, EDMF/ASMF, FDA, GDP, GMP, ISO9001, KDMF, MSDS, USDMF | 14 products |
| LGM Pharma | Distributor | United States | World | BSE/TSE, CEP, CoA, GMP, MSDS, USDMF | 441 products |
| Micro Labs | Producer | India | India | CoA, USDMF | 38 products |
| MSN Organics | Producer | India | India | CoA, GMP, USDMF, WC | 21 products |
| Mylan | Producer | India | India | CoA, GMP, USDMF, WC | 201 products |
| Natco Pharma | Producer | India | India | CoA, USDMF | 40 products |
| PLIVA | Producer | Czech Republic | Croatia | CoA, GMP | 31 products |
| Raks Pharma | Producer | India | India | CoA, USDMF | 58 products |
| Senova Technology Co., Lt... | Producer | China | China | CoA, ISO9001 | 157 products |
| Shilpa Medicare Ltd | Producer | India | India | BSE/TSE, CoA, GMP, ISO9001, MSDS, USDMF, WC | 54 products |
| Sionc Pharma | Producer | India | India | CoA, WC | 10 products |
| Sun Pharma | Producer | India | India | CoA, USDMF | 219 products |
| Torrent Pharma | Producer | India | India | CoA, USDMF | 34 products |
| Unichem Labs. | Producer | India | India | CoA, USDMF | 62 products |
| Vasudha Pharma Chem Ltd. | Producer | India | India | CoA, GMP, MSDS, USDMF, WC | 37 products |
| Yabao Pharma | Producer | China | China | CoA, USDMF | 5 products |
When sending a request, specify which Dimethyl fumarate API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Dimethyl fumarate API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
