2. Academic Validation
  3. Development and therapeutic perspectives of CXCR4 antagonists for disease therapy

Development and therapeutic perspectives of CXCR4 antagonists for disease therapy

  • Eur J Med Chem. 2024 Sep 5:275:116594. doi: 10.1016/j.ejmech.2024.116594.
Jun Yang 1,  Erkang Tian 2,  Li Chen 1,  Zihang Liu 1,  Yijiu Ren 3,  Wuyu Mao 4,  Yiwen Zhang 5,  Jifa Zhang 6
Affiliations

Affiliations

  • 1 Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherapy 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 Clinical 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, Tongji University School of Medicine, Shanghai, 200433, China.
  • 4 Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherapy and Cancer Center and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: [email protected].
  • 5 Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherapy and Cancer Center and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: [email protected].
  • 6 Department of Neurology, Laboratory of Neuro-system and Multimorbidity and State Key Laboratory of Biotherapy and Cancer Center and Institute of Respiratory Health and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: [email protected].
PMID: 38879970 DOI: 10.1016/j.ejmech.2024.116594
Abstract

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.

Keywords

Antagonists; CXCR4; Cancer; Drug design; HIV; Structure-activity relationship.

Figures