Targeted protein degradation (TPD) is a new powerful therapeutic modality which harnesses the body’s natural cellular recycling machinery – the ubiquitin proteasome system (UPS) – to degrade unwanted proteins, and/or break down disease-causing protein complexes. This presentation will highlight the discovery and medicinal chemistry optimization of a series of novel orally bioavailable degraders that target the simultaneous degradation of both IRAK4 and Imid substrates, including Ikaros and Aiolos. These efforts culminated in the identification of KT-413, a heterobifunctional degrader currently being evaluated in Phase I clinical trials. A detailed description of the preclinical pharmacokinetic/pharmacodynamic/efficacy relationships associated with KT-413 will also be described.

Discovery and characterization of potent degraders of IRAK4 and IMiD substrates for oncology indications

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.