Application of DELs for E3 Ligase Ligand Discovery and Targeted Protein Degradation

Targeted protein degradation (TPD) provides new therapeutic opportunities beyond traditional inhibitors. TPD relies on the ability to induce proximity between an E3 ligase and the target of interest, harnessing the ubiquitin proteasome system to ubiquitylate and degrade the target. This proximity can be induced by either monofunctional ligands (molecular glues) or bifunctional molecules that tether ligases and target ligands together. DNA encoded libraries (DELs) provide rapid access to diverse chemical space for ligand discovery and, by their design, facilitate the development of both molecular glues and bifunctional degraders.