<unk>  is a lipophilic, highly mobile molecule in human tissue. As an α,β-unsaturated electrophilic compound,<unk>  is rapidly attacked by the detoxifying agent glutathione (GSH) in a Michael addition reaction. Through these reactions, it is metabolised to monomethyl<unk>  (MMF) prior to entering systemic distribution.<unk>  has been described a prodrug.<unk>  is a precursor of monomethyl<unk> . Other prodrugs that metabolize to monomethyl<unk>  have been developed to treat relapse-remitting multiple sclerosis, including diroximel<unk>  which was approved by the FDA in October 2019. The precise mechanism of action of<unk>  is not clear.<unk>  and MMF can activate the transcription factor (Nuclear factor erythroid-derived 2)-related factor 2 (Nrf2) pathway and MMF has been identified as a nicotinic acid receptor agonist in vitro. In mice that lack Nrf2 expression, however,<unk>  is still able to modulate the immune system, which indicates that Nrf2 is not required for its immunomodulatory action. For psoriasis, the mechanism of action is believed to be due to the interaction of MMF and the intracellular reduced glutathione of cells directly involved in the pathogenesis of psoriasis. The interaction with glutathione leads to the inhibition of nuclear translocation and the transcriptional activity of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). More recently,<unk>  and MMF has been shown to reduce the expression of micro-RNA-21, which is essential for the production of pathogenic cells in multiple sclerosis and psoriasis. This can be achieved because<unk>  and MMF, as cell-permeable metabolites, can epigenetically regulate the expression of micro-RNA-21 via the metabolic-epigenetic interplay in developing immune cells. The main activity of<unk>  and MMF is considered to be immunomodulatory, resulting in a shift in T helper cells (Th) from the Th1 and Th17 profile to a Th2 phenotype. Inflammatory cytokine production is reduced by the induction of proapoptotic events, inhibition of keratinocyte proliferation, reduced expression of adhesion molecules and diminished inflammatory infiltrate within psoriatic plaques. The primary route of elimination is via exhalation of CO2, with small amounts excreted through urine or faeces. There is no evidence for<unk>  interaction with cytochrome P450 and the most common efflux and uptake transporters, and therefore no interactions are expected with medicinal products metabolised or transported by these systems.
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