| Size | Price | Stock | Qty |
|---|---|---|---|
| 500mg |
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| Other Sizes |
| Targets |
Monomethyl fumarate primarily targets the Nrf2 (nuclear factor erythroid 2-related factor 2) pathway. By modifying Keap1 (Kelch-like ECH-associated protein 1), MMF promotes the release and activation of Nrf2. Nrf2 then translocates to the nucleus and binds to antioxidant response elements (AREs), upregulating the expression of various antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione S-transferases. Additionally, MMF has been shown to inhibit the NLRP3 inflammasome and modulate immune responses by affecting dendritic cell differentiation and T-cell polarization.
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| ln Vitro |
With an IC50 of 70 nM, monomethyl fumarate totally prevents the synthesis of cAMP produced by forskolin. With an EC50 of 9.4 μM, monomethyl fumarate causes a dose-dependent Ca2+ signal in GPR109A transfected cells [1]. The cytotoxicity caused by 7β-OHC, which includes inducing cell death, decreasing cell viability, inhibiting cell growth, and disrupting mitochondria, is lessened by monomethyl fumarate (25 μM; 24 hours) [3].
In vitro, monomethyl fumarate exhibits potent cytoprotective and anti-inflammatory effects. It effectively induces Nrf2-dependent gene expression in various cell types, including neurons, astrocytes, and immune cells. MMF has been shown to protect against oxidative stress-induced cell death in neuronal cell lines and primary neurons. In immune cells, MMF inhibits the production of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. It also promotes the differentiation of anti-inflammatory M2 macrophages and regulatory T cells while suppressing pro-inflammatory Th1 and Th17 cell responses. |
| ln Vivo |
In a dose-dependent way, these morphological alterations (photoreceptor loss caused by bright light exposure) are prevented by a single dose of monomethyl fumarate (50–100 mg/kg; i.p.) prior to light exposure [2]. Both oxidative stress and retinal inflammation are decreased by monomethyl fumarate (100 mg/kg). Monomethyl fumarate has the ability to strongly suppress genes that are elevated in light-induced retinopathy (LIR) through the NFkB pathway, including as Tnf-α, Nlrp3, Casp1, and Il-1β[2].
Monomethyl fumarate is the pharmacologically active metabolite of dimethyl fumarate and is responsible for the in vivo efficacy of the parent drug. In animal models of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE), MMF and DMF have demonstrated significant disease-modifying effects, reducing clinical severity, demyelination, and immune cell infiltration into the central nervous system. In models of psoriasis and other inflammatory conditions, MMF has shown anti-inflammatory and tissue-protective effects. The compound's activity is primarily mediated through Nrf2 activation and modulation of immune responses. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for monomethyl fumarate typically involve assessing its ability to modify Keap1 or to activate Nrf2-mediated transcription. Nrf2 activation can be measured using reporter gene assays in cells transfected with an ARE-luciferase construct. The binding of MMF to Keap1 can be studied using surface plasmon resonance or other biophysical techniques. Additionally, the compound's ability to inhibit the NLRP3 inflammasome can be assessed by measuring caspase-1 activation and IL-1β release in LPS-primed macrophages.
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| Cell Assay |
Cellular assays for monomethyl fumarate commonly involve treating various cell types with the compound and measuring Nrf2 activation, antioxidant gene expression, and cytokine production. In neuronal cells, the compound's cytoprotective effects against oxidative stress can be assessed. In immune cells, the effects on cytokine production, T-cell differentiation, and macrophage polarization are typically evaluated. Flow cytometry and ELISA are commonly used to measure these endpoints.
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| Animal Protocol |
Animal/Disease Models: Albino balb/c (Bagg ALBino) mouse (male, 6 weeks old) [2] Doses: 50, 65, 75, 100 mg/kg
Route of Administration: intraperitoneal (ip) injection Experimental Results: These morphological changes were prevented in one dose ( Photoreceptor death induced by bright light exposure)-dependent manner. In vivo animal model protocols for monomethyl fumarate typically involve oral administration of dimethyl fumarate (which is rapidly converted to MMF) or direct administration of MMF to animal models of disease. In the EAE model of multiple sclerosis, the compound is administered daily, and clinical scores, histological analysis of the spinal cord, and immune cell profiling are performed. In models of psoriasis, topical or systemic administration is used, and skin inflammation and histopathology are assessed. |
| ADME/Pharmacokinetics |
Monomethyl fumarate is the major active metabolite of dimethyl fumarate and is responsible for its pharmacological effects. In humans, dimethyl fumarate is rapidly hydrolyzed by esterases to MMF, which then circulates in the plasma. The half-life of MMF is approximately 1 hour. The compound is primarily eliminated via the respiratory route as CO2. Bioavailability of dimethyl fumarate (as MMF) is approximately 40-60% after oral administration.
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| Toxicity/Toxicokinetics |
The toxicological profile of monomethyl fumarate is well-characterized through its use as the active metabolite of dimethyl fumarate. Common adverse effects associated with DMF/MMF include gastrointestinal disturbances (flushing, diarrhea, nausea), which are often managed by dose titration. More serious but rare adverse effects include progressive multifocal leukoencephalopathy (PML), a serious opportunistic infection of the brain, which has been reported in patients treated with dimethyl fumarate. Other potential adverse effects include lymphopenia and elevated liver enzymes.
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| References |
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| Additional Infomation |
Monomethyl fumarate is a dicarboxylic acid monoester formed by the condensation of a carboxyl group of fumarate with methanol. It is a metabolite of dimethyl fumarate and is used to treat patients with relapsing-remitting multiple sclerosis (MS). It can also induce the expression of the NFE2L2 (Nrf2) transcription factor by binding to KEAP1. It has immunomodulatory, antioxidant, and pharmacolytic effects. It is an acrylate, methyl ester, and dicarboxylic acid monoester. Its function is related to that of fumarate. Monomethyl fumarate has been reported in Amesia nigricolor, Rothmannia longiflora, and several other organisms with relevant data. See also: fumarate (containing the active moiety); dimethyl fumarate (active moiety); dimethyl fumarate (active moiety).
Monomethyl fumarate (MMF, CAS# 2756-87-8) is the active metabolite of dimethyl fumarate (DMF, Tecfidera®), a first-line oral therapy for relapsing-remitting multiple sclerosis. MMF is also a key player in the mechanism of action of DMF for the treatment of psoriasis. It is a potent activator of the Nrf2 pathway, leading to the upregulation of antioxidant and cytoprotective genes. The compound is also known to inhibit the NLRP3 inflammasome and modulate immune responses. MMF is available as a research compound for in vitro and in vivo studies. |
| Molecular Formula |
C5H6O4
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|---|---|
| Molecular Weight |
130.0987
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| Exact Mass |
130.026
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| CAS # |
2756-87-8
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| Related CAS # |
Monomethyl fumarate-d3;1616345-41-5;Monomethyl fumarate-d5;1616345-45-9
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| PubChem CID |
5369209
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
250.0±23.0 °C at 760 mmHg
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| Melting Point |
144-145ºC
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| Flash Point |
108.9±16.1 °C
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| Vapour Pressure |
0.0±1.1 mmHg at 25°C
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| Index of Refraction |
1.469
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| LogP |
-0.24
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
9
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| Complexity |
147
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC(=O)/C=C/C(=O)O
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| InChi Key |
NKHAVTQWNUWKEO-NSCUHMNNSA-N
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| InChi Code |
InChI=1S/C5H6O4/c1-9-5(8)3-2-4(6)7/h2-3H,1H3,(H,6,7)/b3-2+
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| Chemical Name |
(E)-4-methoxy-4-oxobut-2-enoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~384.32 mM)
H2O : ~10 mg/mL (~76.86 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (19.22 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (19.22 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 2.5 mg/mL (19.22 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 4: 8.33 mg/mL (64.03 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 7.6864 mL | 38.4320 mL | 76.8640 mL | |
| 5 mM | 1.5373 mL | 7.6864 mL | 15.3728 mL | |
| 10 mM | 0.7686 mL | 3.8432 mL | 7.6864 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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