Dimethyl fumarate

White to off-white powder. Soluble in DMSO (10mg/ml), ethanol (5mg/ml) or DMF (10mg/ml). Sparingly soluble in aqueous buffers. Chemical. CAS: 624-49-7. Formula: C6H8O4. MW: 144.1. Immunomodulatory and anti-inflammatory agent used in patients with relapsing-remitting multiple sclerosis (MS) and psoriasis. Causes an immune switch characterized by induction of anti-inflammatory/regulatory innate and adaptive immune cell populations such as regulatory T cells (Tregs) and inhibition or apoptosis of pro-inflammatory cells, such as T helper 1 (Th1) and Th17 subsets. Blocks immune cell activation through inhibition of glycolysis via post-transcriptional modification (succination) of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in vitro and in vivo and is therefore a useful agent for immunometabolism research. GAPDH catalyzes the conversion of glyceraldehyde 3-phosphate to 1,3-bisphosphoglycerate during glycolysis, an essential metabolic pathway where glucose is converted to pyruvate, to fuel the TCA cycle and oxidative phosphorylation (OXPHOS) for the production of adenosine triphosphate (ATP) as an energy source. GAPDH was previously reported to be succinated on the cysteine-152 in the active site, a modification that leads to the irreversible inactivation of its enzymatic activity. Immunomodulatory effects have been shown on both tissue and immune cells. Possible targets include the engagement of antioxidant responses through activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), inhibition of nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) and engagement with a putative receptor called HCA2. Suppresses NLRP3 inflammasome activation through Nrf2 activation. Anticancer agent. Angiogenesis inhibitor in vitro and in vivo. Blocks NF-kappaB activity in multiple breast cancer cell lines and abrogates NF-kappaB-dependent mammosphere formation, inhibits cell proliferation and significantly impairs xenograft tumor growth. Exerts neuroprotective effects in vivo in experimental autoimmune encephalomyelitis. Has antimicrobial and antifungal activity. Derivative of the TCA cycle intermediate fumarate. Rapidly interacts in a Michael addition reaction with glutathione or is metabolized to monomethyl fumarate.