Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor

I-43: Expression Profile of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway as A Potentional Biomarker in Pathophysiology of Endometriosis

Background MIF via its receptor, CD74, initiates a signaling cascade that leads to proliferation and survival of cells. Also, MIF binding to CD74 activates p38 signaling pathways that lead to positive effect on the expression of COX-2. The aim of this study was to evaluate the gene expression profile of MIF, CD74 and COX-2 in normal, ectopic and eutopic endometrium during menstrual cycle. The e...

Current developments of macrophage migration inhibitory factor (MIF) inhibitors.

The cytokine macrophage migration inhibitory factor (MIF) is regarded as a major regulator of inflammation and a key mediator that counter-regulates the inhibitory effects of glucocorticoids within the immune system. Therefore, MIF is a therapeutic target for the treatment of inflammatory and autoimmune diseases. In addition, MIF was found to be implicated in cancer pathogenesis. Current therap...

Macrophage Migration Inhibitory Factor

A Fluorescence Polarization Assay for Binding to Macrophage Migration Inhibitory Factor and Crystal Structures for Complexes of Two Potent Inhibitors

Human macrophage migration inhibitory factor (MIF) is both a keto-enol tautomerase and a cytokine associated with numerous inflammatory diseases and cancer. Consistent with observed correlations between inhibition of the enzymatic and biological activities, discovery of MIF inhibitors has focused on monitoring the tautomerase activity using l-dopachrome methyl ester or 4-hydroxyphenyl pyruvic a...

Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors

We report the crystal structures of two inhibitors of Plasmodium falciparum macrophage migration inhibitory factor (PfMIF) with nanomolar Ki's, analyze their interactions with the active site of PfMIF, and provide explanations regarding their selectivity of PfMIF versus human MIF. These inhibitors were also found to selectively inhibit interactions between PfMIF and the human MIF receptor CD74....