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PMID: 20971005 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Receptor agonists of macrophage migration inhibitory factor.

Bioorganic & medicinal chemistry letters ·Vol. 20 ·No. 23 ·2010-12-01 ·Pages 7033-6

Jorgensen WL, Gandavadi S, Du X, Hare AA, Trofimov A, Leng L, Bucala R

Abstract

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.

MeSH Terms
Cells, Cultured Click Chemistry Copper Drug Design Fibroblasts/cytology,metabolism Humans Mitogen-Activated Protein Kinase 3/metabolism Phosphorylation/drug effects Protein Binding Receptors, Immunologic/agonists Structure-Activity Relationship Triazoles/pharmacology
Chemicals
Receptors, Immunologic Triazoles macrophage migration inhibitory factor receptor Copper Mitogen-Activated Protein Kinase 3
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Jorgensen William L
Department of Chemistry, Yale University, New Haven, CT 06520, USA. william.jorgensen@yale.edu
Gandavadi Sunilkumar
Du Xin
Hare Alissa A
Trofimov Alexander
Leng Lin
Bucala Richard
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Article Info
Journal
Bioorganic & medicinal chemistry letters
Abbr.
Bioorg Med Chem Lett
ISSN
1464-3405
DOI
10.1016/j.bmcl.2010.09.118
Email
william.jorgensen@yale.edu
Published
2010-12-01
Epub
2010-00-29
Pages
7033-6
Language
English
Region
England
NLM ID
9107377
PMCID
PMC2989669
Subset
IM
Grants
NIAID NIH HHS · AI042310 · United States
NIGMS NIH HHS · R01 GM032136 · United States
NIAMS NIH HHS · R01 AR050498 · United States
NIAMS NIH HHS · R01 AR050498-07 · United States
NIAID NIH HHS · R56 AI042310 · United States
NIGMS NIH HHS · GM032136 · United States
NIAMS NIH HHS · R01 AR049610 · United States
NIAID NIH HHS · R01 AI042310-06 · United States
NIAMS NIH HHS · R01 AR049610-09 · United States
NIAMS NIH HHS · AR049610 · United States
NIAID NIH HHS · R01 AI042310 · United States
NIAMS NIH HHS · AR050498 · United States
NIGMS NIH HHS · R01 GM032136-28 · United States
External Links
PubMed source DOI: 10.1016/j.bmcl.2010.09.118 PMC Full Text View journal details
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