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.
Department of Chemistry, Yale University, New Haven, CT 06520, USA. william.jorgensen@yale.edu
William L
WL
Jorgensen
Sunilkumar
S
Gandavadi
Xin
X
Du
Alissa A
AA
Hare
Alexander
A
Trofimov
Lin
L
Leng
Richard
R
Bucala
D002478:Cells, Cultured; D057930:Click Chemistry; D003300:Copper; D015195:Drug Design; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000819:agonists*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology*
D011971:Receptors, Immunologic; D014230:Triazoles; C033184:macrophage migration inhibitory factor receptor; D003300:Copper; D048052:Mitogen-Activated Protein Kinase 3