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Methyl Fumarate‐Derived Iron Carbonyl Complexes (FumET‐CORMs) as Powerful Anti‐inflammatory Agents

Autoimmune diseases are characterized by dendritic cell (DC)‐driven activation of pro‐inflammatory T cell responses. Therapeutic options for these severe diseases comprise small molecules such as dimethyl fumarate, or “gasotransmitters” such as CO. Herein we describe the synthesis of bifunctional enzyme‐triggered CO‐releasing molecules (ET‐CORMs) that allow the simultaneous intracellular release of both CO and methyl fumarate. Using bone‐marrow‐derived DCs the impressive therapeutic potential of these methyl fumarate‐derived compounds (FumET‐CORMs) is demonstrated by strong inhibition of lipopolysaccharide‐induced pro‐inflammatory signaling pathways and blockade of downstream interleukin‐12 or ‐23 production. The data also show that FumET‐CORMs are able to transform DCs into an anti‐inflammatory phenotype. Thus, these novel compounds have great clinical potential, for example, for the treatment of psoriasis or other inflammatory conditions of the skin.