白细胞介素-1受体相关激酶4小分子抑制剂的研究进展  

Recent advances in small molecule inhibitors of interleukin-1 receptor-associated kinase

作　　者：余竞成 董正川 穆瑞旭 陈乐园 李祎亮[3] 侯文彬 YU Jing-cheng;DONG Zheng-chuan;MU Rui-xu;CHEN Le-yuan;LI Yi-liang;HOU Wen-bin(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Chase Sun Pharmaceutical Co.,Ltd.,Tianjin 301700,China;Institute of Radiation Medicine,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300192,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津红日药业股份有限公司,天津301700 [3]中国医学科学院、北京协和医学院放射医学研究所,天津300192

出　　处：《药学学报》2023年第1期27-38,共12页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金青年项目资助(82104012);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资助(2021-I2M-1-042)。

摘　　要：白细胞介素-1受体相关激酶4 (interleukin-1 receptor associated kinase 4, IRAK-4)作为一种丝氨酸-苏氨酸激酶,是转导IL-1R家族和TLRs信号通路的关键信号节点。研究发现IRAK-4介导的炎症通路可以引起人体的关节、肠道、肝脏和神经系统的炎症反应及其他自身免疫疾病,也是一些癌症细胞的耐药性原因。因此, IRAK-4可以作为炎症疾病和癌症的有效治疗靶点。研发结构新颖的IRAK-4小分子抑制剂,考察其安全性和有效性,丰富对炎症和癌症疾病的临床治疗用药,是该通路药物发展的方向。本文按不同结构分类概述了关于IRAK-4信号通路小分子抑制剂的最新研究进展,旨在为相关药物的研发工作提供参考。Interleukin-1 receptor associated kinase 4(IRAK-4),acting as a serine threonine kinase,is considered as a key signal node for the transduction of IL-1R family and TLRs signal pathway.Studies have found that IRAK-4has a hand in many signal pathways,involving the inflammatory response of human joints,intestines,liver and nervous system,as well as other autoimmune diseases.It is also one of the causes of drug resistance of some cancer cells.Therefore,IRAK-4 tends to be an effective therapeutic target for inflammatory diseases and cancer.The prospects for the development of drugs in this pathway is to develop novel IRAK-4 small molecule inhibitors and investigate their safety and effectiveness,enrich the clinical treatment of inflammatory and cancer diseases finally.This paper classified and summarized the latest research progress on small molecule inhibitors of IRAK-4signaling pathway according to structures of the compounds,in order to provide assistances and references for the research and development of related drugs.

关 键 词：白细胞介素-1受体相关激酶4 TLRs/IL-1R信号通路 炎症性疾病 抗肿瘤 小分子抑制剂 

分 类 号：R914[医药卫生—药物化学]