Small molecule inhibitors of macrophage migration inhibitory factor (MIF) as emerging class of therapeutics for immune disorders

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• MIF plays a key part in inflammatory diseases and cancer. • Many structural scaffolds are available for MIF inhibition. • Not all studies provide proper assessment of MIF inhibitory potency. • MIF tautomerase activity does not obey standard Michelis–Menten enzyme kinetics.

 Macrophage migration inhibitory factor (MIF) is an important cytokine for which an increasing number of functions is being described in the pathogenesis of inflammation and cancer. Nevertheless, the availability of potent and druglike MIF inhibitors that are well-characterized in relevant disease models remains limited. Development of highly potent and selective small-molecule MIF inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we provide an overview of recent advances in the identification of MIF as a pharmacological target in the pathogenesis of inflammatory diseases and cancer. We also give an overview of the current developments in the discovery and design of small-molecule MIF inhibitors and define future aims in this field.

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