Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associa...Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associated with several inflammatory diseases or cancer.Therefore,targeting IRAK4 has emerged as a promising therapeutic strategy.A range of potent and selective IRAK4 inhibitors and degraders based on draggability have been designed and developed.This article provides a comprehensive summary of the IRAK4 inhibitors and degraders that have been developed and discusses the challenges and opportunities for research in this area.展开更多
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 pathwa...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.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82293684,82293680)the National Key R&D Program of China(No.2020YFA0908004)CAMS Innovation Fund for Medical Science of China(No.2022-I2M-1-014)。
文摘Interleukin-1 receptor-associated kinase 4(IRAK4)is a key kinase downstream of the interleukin-1 receptor(IL-1R)and Toll-like receptors(TLRs)signaling pathway,whose overexpression and hyperactivation have been associated with several inflammatory diseases or cancer.Therefore,targeting IRAK4 has emerged as a promising therapeutic strategy.A range of potent and selective IRAK4 inhibitors and degraders based on draggability have been designed and developed.This article provides a comprehensive summary of the IRAK4 inhibitors and degraders that have been developed and discusses the challenges and opportunities for research in this area.
基金supported by the National Natural Science Foundation of China(82293684 and 82293680)the National Key R&D Program of China(2020YFA0908004)CAMS Innovation Fund for Medical Science of China(2022-I2M-1-014).
文摘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.
