Yaoxiang Lin, Lulu Zheng, Ying Xu, Xinyan Wang, Jie Li, Lei Zheng*, Guang Liang* and Lingfeng Chen*,
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Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) Degraders for Treating Inflammatory Diseases: Advances and Prospects
Interleukin-1 receptor-associated kinase 4 (IRAK4) is involved in various inflammation-related diseases. Both the kinase and scaffolding functions of IRAK4 initiate pro-inflammatory factor transcription and expression. The scaffolding function of IRAK4 is essential for Myddosome assembly and NF-κB activation. Conventional small-molecule inhibitors effectively inhibit the kinase function of IRAK4 but do not block its scaffolding function. Recently, various IRAK4 degraders have shown promising therapeutic potential in inflammatory diseases. The most advanced IRAK4-selective degrader, KT-474 (SAR444656), significantly reduced inflammatory biomarker levels in patients and demonstrated high safety and tolerability. This perspective introduces and discusses the physiological biology of IRAK4, its associated diseases, and the current development of IRAK4 degraders, thereby offering insights into future research directions.
期刊介绍：
The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents.
The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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