Receptor agonists of macrophage migration inhibitory factor

被引：45

作者：

Jorgensen, William L. ^{[1
]}

Gandavadi, Sunilkumar ^{[1
]}

Du, Xin ^{[2
]}

Hare, Alissa A. ^{[1
]}

Trofimov, Alexander ^{[1
]}

Leng, Lin ^{[2
]}

Bucala, Richard ^{[2
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 23期

基金：

美国国家卫生研究院;

关键词：

MIF; Cytokine; Agonists; Structure-based design; AMPK activation; ERK phosphorylation; Click chemistry; ACTIVATED PROTEIN-KINASE; PHENYLPYRUVATE TAUTOMERASE ACTIVITY; FACTOR MIF TAUTOMERASE; ANTIINFLAMMATORY AGENTS; TERMINAL ALKYNES; DISCOVERY; OPTIMIZATION; ANTAGONISTS; BINDING; GROWTH;

D O I：

10.1016/j.bmcl.2010.09.118

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2010 Elsevier Ltd. All rights reserved.

引用

收藏

页码：7033 / 7036

页数：4

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