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STATs,治疗自身免疫性和炎症性疾病的有前途的靶点。

STATs, promising targets for the treatment of autoimmune and inflammatory diseases.

机构信息

Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China; Institute of Immunology and Inflammation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.

Laboratory of Human Diseases and Immunotherapy, and State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

Eur J Med Chem. 2024 Nov 5;277:116783. doi: 10.1016/j.ejmech.2024.116783. Epub 2024 Aug 17.

Abstract

Cytokines play a crucial role in the pathophysiology of autoimmune and inflammatory diseases, with over 50 cytokines undergoing signal transduction through the Signal Transducers and Activators of Transcription (STAT) signaling pathway. Recent studies have solidly confirmed the pivotal role of STATs in autoimmune and inflammatory diseases. Therefore, this review provides a detailed summary of the immunological functions of STATs, focusing on exploring their mechanisms in various autoimmune and inflammatory diseases. Additionally, with the rapid advancement of structural biology in the field of drug discovery, many STAT inhibitors have been identified using structure-based drug design strategies. In this review, we also examine the structures of STAT proteins and compile the latest research on STAT inhibitors currently being tested in animal models and clinical trials for the treatment of immunological diseases, which emphasizes the feasibility of STATs as promising therapeutic targets and provides insights into the design of the next generation of STAT inhibitors.

摘要

细胞因子在自身免疫和炎症性疾病的病理生理学中起着至关重要的作用,超过 50 种细胞因子通过信号转导和转录激活因子(STAT)信号通路进行信号转导。最近的研究确凿地证实了 STAT 在自身免疫和炎症性疾病中的关键作用。因此,本综述详细总结了 STAT 的免疫学功能,重点探讨了它们在各种自身免疫和炎症性疾病中的作用机制。此外,随着药物发现领域结构生物学的快速发展,许多 STAT 抑制剂已通过基于结构的药物设计策略被识别出来。在本综述中,我们还研究了 STAT 蛋白的结构,并汇编了目前正在动物模型和临床试验中测试用于治疗免疫性疾病的 STAT 抑制剂的最新研究,这强调了 STAT 作为有前途的治疗靶点的可行性,并为下一代 STAT 抑制剂的设计提供了思路。

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