Protein kinases: drug targets for immunological disorders.
Protein kinases: drug targets for immunological disorders.
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DOI：
10.1038/s41577-023-00877-7
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发表时间：
2023-12
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影响因子：
--
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中科院分区：
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--
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蛋白激酶在细胞活化过程中发挥重要作用，包括多种免疫受体的信号转导。鉴于它们在细胞生长和死亡以及炎症介质产生中的作用，靶向激酶已被证明是一种有效的治疗策略，最初作为抗癌疗法，但不久之后用于免疫介导性疾病。在此，我们概述了专门针对与免疫细胞功能相关的蛋白激酶而产生的小分子抑制剂的现状，重点是那些被批准用于治疗免疫介导性疾病的小分子抑制剂。针对细胞因子受体信号传导的Janus激酶抑制剂的开发一直是一个特别活跃的领域，Janus激酶抑制剂已被批准用于治疗多种自身免疫性疾病和过敏性疾病以及COVID-19。此外，靶向抗原受体信号传导的TEC家族激酶抑制剂（包括布鲁顿酪氨酸激酶抑制剂）已被批准用于血液系统恶性肿瘤和移植物抗宿主病。这一经验提供了关于选择性的重要性（或不重要性）以及遗传信息告知有效性和安全性的限制的多个重要教训。许多新的药物和靶向激酶的新方法正在产生。靶向蛋白激酶的药物已经对癌症的治疗产生了重大影响，现在也被证明对许多免疫疾病有益。这篇综述描述了它们的临床应用，重点是Janus激酶抑制剂，以及它们如何告知疾病的机制，以及它们如何进化以提高疗效和安全性。
Protein kinases play a major role in cellular activation processes, including signal transduction by diverse immunoreceptors. Given their roles in cell growth and death and in the production of inflammatory mediators, targeting kinases has proven to be an effective treatment strategy, initially as anticancer therapies, but shortly thereafter in immune-mediated diseases. Herein, we provide an overview of the status of small molecule inhibitors specifically generated to target protein kinases relevant to immune cell function, with an emphasis on those approved for the treatment of immune-mediated diseases. The development of inhibitors of Janus kinases that target cytokine receptor signalling has been a particularly active area, with Janus kinase inhibitors being approved for the treatment of multiple autoimmune and allergic diseases as well as COVID-19. In addition, TEC family kinase inhibitors (including Bruton’s tyrosine kinase inhibitors) targeting antigen receptor signalling have been approved for haematological malignancies and graft versus host disease. This experience provides multiple important lessons regarding the importance (or not) of selectivity and the limits to which genetic information informs efficacy and safety. Many new agents are being generated, along with new approaches for targeting kinases. Drugs that target protein kinases have had a major impact on the treatment of cancer and now are proving beneficial in numerous immunological diseases. This Review describes their clinical application, with a focus on Janus kinase inhibitors, and how they inform mechanisms of disease and have evolved to improve efficacy and safety.
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影响因子：
3.4
作者：
Chimalakonda A;Burke J;Cheng L;Catlett I;Tagen M;Zhao Q;Patel A;Shen J;Girgis IG;Banerjee S;Throup J
通讯作者：
Throup J
影响因子：
64.5
作者：
O'Shea JJ;Kanno Y;Chan AC
通讯作者：
Chan AC
DOI：
10.7759/cureus.11701
发表时间：
2020-11-25
期刊：
Cureus
影响因子：
--
作者：
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通讯作者：
Howell D
影响因子：
4.8
作者：
Arter, Chris;Trask, Luke;Ward, Sarah;Yeoh, Sharon;Bayliss, Richard
通讯作者：
Bayliss, Richard
影响因子：
5.3
作者：
Tefferi A
通讯作者：
Tefferi A