Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Harnessing the ubiquitin proteasome system to degrade proteins of interest offers potential to modulate previously undruggable targets. The field of protein degraders has been generating much interest in recent years with many molecules entering the clinic, both molecular glues and heterobifunctional degraders that contain an E3 ligase binding domain and a target binding domain connected by a linker. Heterobifunctional degraders have some unique properties that will be discussed, including such as the catalytic nature, physical properties that can impact drug discovery testing, and the potential for decreased degradation at high drug concentrations. In addition, while the nonclinical toxicology assessment for protein degraders (either molecular glues or heterobifunctional targeted protein degraders) shares the same principles as for classical small molecules, there are some additional considerations due to the modality. This presentation will discuss the challenges and opportunities for these exciting molecules and current practices across the industry for in vitro and in vivo nonclinical safety assessments for heterobifunctional protein degraders. Approaches for selecting a toxicologically relevant species for in vivo studies will also be discussed.
