药学学报, 2021, 56(9): 2472-2484
引用本文:
赵丽萍, 宋丹青, 汪燕翔*. IL-6/STAT3信号通路小分子抑制剂的研究进展[J]. 药学学报, 2021, 56(9): 2472-2484.
ZHAO Li-ping, SONG Dan-qing, WANG Yan-xiang*. Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway[J]. Acta Pharmaceutica Sinica, 2021, 56(9): 2472-2484.

IL-6/STAT3信号通路小分子抑制剂的研究进展
赵丽萍, 宋丹青, 汪燕翔*
中国医学科学院、北京协和医学院医药生物技术研究所, 北京 100050
摘要:
IL-6作为一种多效性的细胞因子,在体内参与多种生理活动。IL-6通过多种机制在慢性炎症、自身免疫性疾病、肿瘤等疾病的生理和病理过程中发挥着重要作用,目前IL-6/IL-6R靶向抑制剂已被证明能够改善类风湿性关节炎、全身型幼年特发性关节炎等部分炎症性疾病。IL-6与特定受体结合后激活下游JAK/STAT3信号通路,异常激活的STAT3常出现在多种类型的恶性肿瘤中,参与肿瘤的发生和发展。另外,有研究表明IL-6为COVID-19患者相关的细胞因子风暴中的关键因子。IL-6/STAT3通路在多个复杂疾病中的生理参与过程使得该通路成为药物发现的研究热点,本文概述了关于IL-6/STAT3信号通路小分子抑制剂的最新研究进展,尤以2017年后为主,旨在为之后相关药物的研发工作提供参考。
关键词:    IL-6      STAT3      炎症性疾病      抗肿瘤      小分子抑制剂     
Advances in small molecular inhibitors of IL-6/STAT3 signaling pathway
ZHAO Li-ping, SONG Dan-qing, WANG Yan-xiang*
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
As a pleiotropic cytokine, interleukin-6 (IL-6) participates in many physiological activities in vivo. IL-6 plays an important role in the physiology and pathology of chronic inflammation, autoimmune diseases, tumors and other diseases through diverse mechanisms. At present, inhibitors targeting IL-6/IL-6R have been shown to improve treatments for some inflammatory diseases such as rheumatoid arthritis and systemic juvenile idiopathic arthritis. IL-6 binds to a specific receptor to activate the downstream JAK/STAT3 signaling pathway. However abnormally activated STAT3 often appears in various types of malignant tumors and participates in the occurrence and development of tumors. In addition, studies have shown that IL-6 is a key factor in the cytokine storm associated with COVID-19 patients. The physiological participation of IL-6/STAT3 pathway in complex diseases makes this pathway become a research hotspot for drug discovery. Therefore, we summarize the latest research progress of small molecular inhibitors on IL-6/STAT3 signaling pathway, in order to provide a reference for the development of IL-6/STAT3 related drug in the future.
Key words:    interleukin-6    signal transducer and activator of transcription 3    inflammatory diseases    antitumor    small molecular inhibitor   
收稿日期: 2021-02-17
DOI: 10.16438/j.0513-4870.2021-0233
基金项目: 中国医学科学院医学与健康科技创新工程重大协同创新项目(2020-I2M-2-010).
通讯作者: 汪燕翔,Tel:86-10-63033012,E-mail:wangyanxiang@imb.pumc.edu.cn
Email: wangyanxiang@imb.pumc.edu.cn
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