Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer.
10.1016/j.apsb.2024.09.008
- Author:
Yifan FENG
1
;
Chengjuan CHEN
1
;
Anqi SHAO
2
;
Lei WU
1
;
Haiyu HU
1
;
Tiantai ZHANG
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
2. Department of Dermatology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
- Publication Type:Review
- Keywords:
Autoimmune diseases;
Cancer;
Degraders;
IL-1R/TLRs signal pathway;
IRAK4;
IRAK4 inhibitors;
NF-κB
- From:
Acta Pharmaceutica Sinica B
2024;14(12):5091-5105
- CountryChina
- Language:English
-
Abstract:
Interleukin-1 receptor-related kinase (IRAK4) is a widely expressed serine/threonine kinase involved in the regulation of innate immunity. IRAK4 plays a pivotal role as a key kinase within the downstream signaling pathway cascades of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs). The signaling pathways orchestrated by IRAK4 are integral to inflammatory responses, and its overexpression is implicated in the pathogenesis of inflammatory diseases, autoimmune disorders, and cancer. Consequently, targeting IRAK4-mediated signaling pathways has emerged as a promising therapeutic strategy. Small molecule inhibitors and degraders designed to modulate IRAK4 have shown efficacy in mitigating related diseases. In this paper, we will provide a detailed description of the structure and function of IRAK4, the role of IRAK4 in related diseases, as well as the currently reported small molecule inhibitors and degraders of IRAK4. It is expected to provide new directions for enriching the clinical treatment of inflammation and related diseases.
