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The chemical diversity and structure-based evolution of non-peptide CXCR4 antagonists with diverse therapeutic potential.

Abstract：

:The CXC chemokine receptor 4 (CXCR4) is a highly reserved G-protein coupled 7-transmembrane (TM) chemokine receptor which consists of 352 amino acids. CXCR4 has only one endogenous chemokine ligand of CXCL12, besides several other natural nonchemokine ligands such as extracellular ubiquitin and noncognate ligand of MIF. CXCR4 strongly binds to CXCL12 and the resulting CXCLl2/CXCR4 axis is the molecular basis of their various biological functions, which include: (1) mediating immune and inflammatory response; (2) regulation of hematopoietic stem cell migration and homing; (3) an essential co-receptor for HIV entry into host cells; (4) participation in the process of embryonic development; (5) malignant tumor invasion and metastasis; (6) myocardial infarction, ischemic stroke and acute kidney injury. Correspondingly, CXCR4 antagonists find potential therapeutic applications in HIV infection, as well as hematopoietic stem cell migration, inflammation, immune-related diseases, tumor and ischemic diseases. Recently, great achievements have been made and a number of non-peptide CXCR4 antagonists with diversity scaffolds have been discovered. In this review, the discovery of small molecule CXCR4 antagonists focused on the structures, activities, evolution and development of representative CXCR4 antagonists is comprehensively described. The central role of CXCR4 in diverse cellular signaling pathways and its involvement in several diseases progressions are discussed as well.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Peng D,Cao B,Zhou YJ,Long YQ

doi

10.1016/j.ejmech.2018.02.043

subject

Has Abstract

pub_date

2018-04-10 00:00:00

pages

148-169

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(18)30173-9

journal_volume

149

pub_type

杂志文章,评审

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