Receptor agonists of macrophage migration inhibitory factor

The cytokine MIF is involved in inflammation and cell proliferation via pathways initiated by its binding to the transmembrane receptor CD74. MIF also promotes AMPK activation with potential benefits for response to myocardial infarction and ischemia-reperfusion. Structure-based molecular design has led to the discovery of not only antagonists, but also the first agonists of MIF–CD74 binding. The compounds contain a triazole core that is readily assembled via Cu-catalyzed click chemistry. The agonist and antagonist behaviors were confirmed via study of MIF-dependent ERK1/2 phosphorylation in human fibroblasts.

Graphical abstractSubstituted aryl-1,2,3-triazoles are reported as the first agonists of the binding of the cytokine macrophage migration inhibitory factor (MIF) to its receptor CD74. The contrasting behavior of MIF antagonists and agonists is also demonstrated in MIF-dependent ERK1/2 phosphorylation using human fibroblasts.Figure optionsDownload full-size imageDownload as PowerPoint slide