588 Identification of highly potent and selective Interleukin-1 receptor associated kinase 4 (IRAK4) degraders for the treatment of hidradenitis suppurativa

Abstract

Interleukin-1 receptor associated kinase 4 (IRAK4) plays a central role in myddosome signaling via kinase and scaffolding functions, making it an attractive target for the treatment of TLR- and IL-1R-driven inflammatory diseases. IL-1 family cytokines and TLRs, are central to the pathophysiology of hidradenitis suppurativa (HS), a Th1- and Th17-mediated neutrophilic, chronic inflammatory skin disease. Kymera has developed orally administered hetero-bifunctional molecules that selectively target IRAK4 for degradation and elimination by the ubiquitin proteasome pathway.