The chemical diversity and structure-based evolution of non-peptide CXCR4 antagonists with diverse therapeutic potential.
The chemical diversity and structure-based evolution of non-peptide CXCR4 antagonists with diverse therapeutic potential.
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具有不同治疗潜力的非肽 CXCR4 拮抗剂的化学多样性和基于结构的进化。
DOI：
10.1016/j.ejmech.2018.02.043
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发表时间：
2018
影响因子：
6.7
通讯作者：
Y. Long
中科院分区：
文献类型：
--
作者：
Dian Peng;B. Cao;Ying;Y. Long
CXC趋化因子受体4（CXCR 4）是由352个氨基酸组成的高度保留的G蛋白偶联的7-跨膜（TM）趋化因子受体。CXCR 4除了具有多种天然的非趋化因子配体（如细胞外泛素和MIF的非同源配体）外，仅具有CXCL 12的一个内源性趋化因子配体。CXCR 4与CXCL 12结合强烈，产生的CXCL 12/CXCR 4轴是其多种生物学功能的分子基础，包括：（1）介导免疫和炎症反应;（2）调节造血干细胞迁移和归巢;（3）HIV进入宿主细胞的必需辅助受体;（4）参与胚胎发育过程;（5）恶性肿瘤的侵袭和转移;（6）心肌梗死、缺血性脑卒中和急性肾损伤。相应地，CXCR 4拮抗剂在HIV感染以及造血干细胞迁移、炎症、免疫相关疾病、肿瘤和缺血性疾病中发现潜在的治疗应用。近年来，CXCR 4拮抗剂的研究取得了很大的进展，发现了一批具有不同骨架的非肽类CXCR 4拮抗剂。本文综述了近年来发现的CXCR 4拮抗剂的结构、活性、进化和发展。还讨论了CXCR 4在多种细胞信号传导途径中的核心作用及其与多种疾病进展的关系。
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.
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影响因子：
6.7
作者：
Bai R;Shi Q;Liang Z;Yoon Y;Han Y;Feng A;Liu S;Oum Y;Yun CC;Shim H
通讯作者：
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影响因子：
15
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影响因子：
6.7
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影响因子：
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