School of Pharmacy, University of East Anglia, Norwich, U.K.
Biochem Soc Trans. 2021 Jun 30;49(3):1385-1395. doi: 10.1042/BST20201114.
The chemokine system plays a fundamental role in a diverse range of physiological processes, such as homeostasis and immune responses. Dysregulation in the chemokine system has been linked to inflammatory diseases and cancer, which renders chemokine receptors to be considered as therapeutic targets. In the past two decades, around 45 drugs targeting chemokine receptors have been developed, yet only three are clinically approved. The challenging factors include the limited understanding of aberrant chemokine signalling in malignant diseases, high redundancy of the chemokine system, differences between cell types and non-specific binding of the chemokine receptor antagonists due to the broad ligand-binding pockets. In recent years, emerging studies attempt to characterise the chemokine ligand-receptor interactions and the downstream signalling protein-protein interactions, aiming to fine tuning to the promiscuous interplay of the chemokine system for the development of precision medicine. This review will outline the updates on the mechanistic insights in the chemokine system and propose some potential strategies in the future development of targeted therapy.
趋化因子系统在多种生理过程中发挥着基本作用，如体内平衡和免疫反应。趋化因子系统的失调与炎症性疾病和癌症有关，这使得趋化因子受体被认为是治疗靶点。在过去的二十年中，已经开发了大约 45 种针对趋化因子受体的药物，但只有三种在临床上得到批准。具有挑战性的因素包括对恶性疾病中异常趋化因子信号的了解有限、趋化因子系统的高度冗余、细胞类型之间的差异以及由于广泛的配体结合口袋而导致的趋化因子受体拮抗剂的非特异性结合。近年来，新兴的研究试图描述趋化因子配体-受体相互作用和下游信号蛋白-蛋白相互作用，旨在对趋化因子系统的混杂相互作用进行微调，以开发精准医学。这篇综述将概述趋化因子系统的机制研究进展，并提出未来靶向治疗的一些潜在策略。
