Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy.
Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy.
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DOI：
10.18632/oncotarget.26058
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发表时间：
2018-09-07
期刊：
影响因子：
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通讯作者：
Agarwal A
中科院分区：
文献类型：
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作者：
Singer JW;Fleischman A;Al-Fayoumi S;Mascarenhas JO;Yu Q;Agarwal A
Interleukin-1 受体相关激酶（IRAK1、IRAK2、IRAK3 [IRAK-M] 和 IRAK4）是参与 Toll 样受体和 ILAK-1 信号通路的丝氨酸-苏氨酸激酶，通过该通路调节先天免疫和炎症。有证据表明，IRAK 在癌症、代谢和炎症性疾病的病理生理学中发挥着关键作用，并且 IRAK 抑制具有潜在的治疗益处。能够选择性干扰IRAK功能和表达的分子已被报道，为IRAK抑制的临床评估铺平了道路。在此，我们重点关注IRAK1，回顾其结构和生理作用，并总结IRAK1抑制剂在临床前和临床研究中的新数据。
Interleukin-1 receptor-associated kinases (IRAK1, IRAK2, IRAK3 [IRAK-M], and IRAK4) are serine-threonine kinases involved in toll-like receptor and interleukin-1 signaling pathways, through which they regulate innate immunity and inflammation. Evidence exists that IRAKs play key roles in the pathophysiologies of cancers, and metabolic and inflammatory diseases, and that IRAK inhibition has potential therapeutic benefits. Molecules capable of selectively interfering with IRAK function and expression have been reported, paving the way for the clinical evaluation of IRAK inhibition. Herein, we focus on IRAK1, review its structure and physiological roles, and summarize emerging data for IRAK1 inhibitors in preclinical and clinical studies.