Huo Rongrong, Jiang Yu, Zhang Li, Du Shufang, Zhou Dan
State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Jul 25;16:1556196. doi: 10.3389/fphar.2025.1556196. eCollection 2025.
CXC chemokine receptor 3 (CXCR3) is a G protein-coupled chemokine receptor that plays a key role in regulating immune responses and is involved in various pathological processes, particularly in tumor development and inflammatory diseases, making it a novel target for clinical therapy. The expression of CXCR3 and its ligands-CXCL9, CXCL10, CXCL11, CXCL4, and CXCL4L1-is closely associated with the onset and progression of numerous diseases. With a deeper understanding of the mechanisms underlying CXCR3 function, significant progress has been made in the development of small molecule antagonists targeting CXCR3, some of which have entered clinical trials and demonstrated therapeutic potential. This review provides an overview of the structure and signaling pathways of CXCR3, its biological functions in cancer and inflammatory diseases, and highlights the innovative roles of CXCR3 in these diseases. Furthermore, it discusses recent advances in the development of small molecule antagonists, particularly those that have been tested in clinical settings, such as AMG 487 and ACT-777991. These studies provide a scientific foundation for the development of novel CXCR3 antagonists and may offer new directions for future clinical treatments.
CXC趋化因子受体3（CXCR3）是一种G蛋白偶联趋化因子受体，在调节免疫反应中起关键作用，并参与各种病理过程，尤其是肿瘤发展和炎症性疾病，使其成为临床治疗的新靶点。CXCR3及其配体——CXCL9、CXCL10、CXCL11、CXCL4和CXCL4L1的表达与多种疾病的发生和进展密切相关。随着对CXCR3功能潜在机制的深入了解，在开发靶向CXCR3的小分子拮抗剂方面取得了重大进展，其中一些已进入临床试验并显示出治疗潜力。本文综述了CXCR3的结构和信号通路、其在癌症和炎症性疾病中的生物学功能，并强调了CXCR3在这些疾病中的创新作用。此外，还讨论了小分子拮抗剂开发的最新进展，特别是那些已在临床环境中进行测试的拮抗剂，如AMG 487和ACT-777991。这些研究为新型CXCR3拮抗剂的开发提供了科学依据，并可能为未来的临床治疗提供新方向。
