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Development and therapeutic perspectives of CXCR4 antagonists for disease therapy

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机构： [1]Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherqpy and Cancer Center and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Oral Diseases, National Cinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China [3]Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongi University School of Medicine, Shanghai, 200433, China

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关键词： CXCR4 Antagonists HIV Cancer Drug design Structure-activity relationship

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Chemokine receptor 4 (CXCR4) is a subtype receptor protein of the GPCR family with a seven-transmembrane structure widely distributed in human tissues. CXCR4 is involved in diseases (e.g., HIV-1 infection), cancer proliferation and metastasis, inflammation signaling pathways, and leukemia, making it a promising drug target. Clinical trials on CXCR4 antagonists mainly focused on peptides and antibodies, with a few small molecule compounds, such as AMD11070 (2) and MSX-122 (3), showing promise in cancer treatment. This perspective discusses the structure-activity relationship (SAR) of CXCR4 and its role in diseases, mainly focusing on the SAR of CXCR4 antagonists. It also explores the standard structural features and target interactions of CXCR4 binding in different disease categories. Furthermore, it investigates various modification strategies to propose potential improvements in the effectiveness of CXCR4 drugs.Copyright © 2024 Elsevier Masson SAS. All rights reserved.

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大类 | 2 区

医学

小类 | 1 区药物化学

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第一作者机构： [1]Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherqpy and Cancer Center and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

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