Recent advances in interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors and PROTACs

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. IRAK4 is a key kinase of the IL-1R/TLRs signaling pathway, targeting IRAK4 has emerged as a promising therapeutic strategy. Structurally diverse IRAK4 inhibitors or degraders have been designed and developed.