The recent advance of Interleukin-1 receptor associated kinase 4 inhibitors for the treatment of inflammation and related diseases

被引：18

作者：

Bai, Yi-Ru ^{[1
,2
]}

Yang, Wei-Guang ^{[1
]}

Hou, Xue-Hui ^{[3
]}

Shen, Dan-Dan ^{[4
]}

Zhang, Sheng-Nan ^{[1
]}

Li, Yan ^{[1
]}

Qiao, Yan-Yan ^{[1
]}

Wang, Sai-Qi ^{[5
,6
]}

Yuan, Shuo ^{[1
,2
]}

Liu, Hong-Min ^{[2
]}

机构：

[1] Zhengzhou Univ, Childrens Hosp, Henan Childrens Hosp, Zhengzhou Childrens Hosp, Zhengzhou 450018, Peoples R China

[2] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China

[3] Henan Univ Anim Husb & Econ, Fac Sci, Zhengzhou 450046, Peoples R China

[4] Zhengzhou Univ, Affiliated Hosp 3, Dept Obstet & Gynecol, Zhengzhou Key Lab Endometrial Dis Prevent & Treatm, Zhengzhou 450052, Peoples R China

[5] Zhengzhou Univ, Affiliated Canc Hosp, Zhengzhou 450008, Peoples R China

[6] Henan Canc Hosp, Henan Engn Res Ctr Precis Therapy Gastrointestinal, Zhengzhou Key Lab Precis Therapy Gastrointestinal, Zhengzhou 450008, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 258卷

基金：

中国国家自然科学基金;

关键词：

The interleukin-1 receptor associated kinase 4; inhibitors; Inflammatory diseases; Anticancer; Autoimmune diseases; PROTAC; IRAK-4; INHIBITORS; DISCOVERY; INNATE; POTENT; IDENTIFICATION; DESIGN; MACROCYCLIZATION; OPTIMIZATION; DEGRADER;

D O I：

10.1016/j.ejmech.2023.115606

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The interleukin-1 receptor associated kinase 4 (IRAK-4) is a member of serine-threonine kinase family, which plays an important role in the regulation of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs) related signaling pathways. At present, the IRAK-4 mediated inflammation and related signaling pathways contribute to inflammation, which are also responsible for other autoimmune diseases and drug resistance in cancers. Therefore, targeting IRAK-4 to develop single-target, multi-target inhibitors and proteolysis-targeting chimera (PROTAC) degraders is an important direction for the treatment of inflammation and related diseases. Moreover, insight into the mechanism of action and structural optimization of the reported IRAK-4 inhibitors will provide the new direction to enrich the clinical therapies for inflammation and related diseases. In this comprehensive review, we introduced the recent advance of IRAK-4 inhibitors and degraders with regards to structural optimization, mechanism of action and clinical application that would be helpful for the development of more potent chemical entities against IRAK-4.

引用

页数：21

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