tipasertideg

Tipasertideg (also known as IRW-1080, KT-474, KYM-001, and SAR444656) is a first-in-class, orally bioavailable proteolysis-targeting chimera (PROTAC) designed to selectively degrade interleukin-1 receptor-associated kinase 4 (IRAK4). Developed by Kymera Therapeutics in collaboration with Sanofi, tipasertideg functions by recruiting the E3 ubiquitin ligase cereblon (CRBN) to target IRAK4 for ubiquitination and subsequent proteasomal degradation. IRAK4 is a key scaffolding kinase in the myddosome complex that mediates signaling downstream of interleukin-1 receptors (IL-1R) and Toll-like receptors (TLRs), which are critical drivers of immune-inflammatory pathways. By completely degrading IRAK4, tipasertideg abolishes both its kinase and scaffolding functions, offering a broader anti-inflammatory effect than traditional kinase inhibitors. Tipasertideg was evaluated in Phase 2 clinical trials for the treatment of moderate-to-severe hidradenitis suppurativa (HS) and atopic dermatitis (AD). However, in June 2025, Sanofi decided to discontinue the clinical development of tipasertideg in favor of a second-generation, more potent and selective IRAK4 degrader, KT-485 (SAR447971). Additionally, tipasertideg has been investigated in preclinical models of acute kidney injury (AKI) and B-cell malignancies.

Other names

tipasertideg