Protein Induced Degradation: Druggability Strategy

This lecture discusses protein-induced degradation as a strategy to enhance target druggability by creating a ternary complex between a protein target and an E3 ubiquitin ligase. It covers the limitations of the occupancy-driven paradigm in drug development, the mechanism of PROTACS in enhancing target druggability, and the process of ubiquitin attachment to proteins. The lecture also explores the use of phthalimide conjugation for in vivo target protein degradation and the effects of dBET1 at the proteome level. Additionally, it delves into the design and advantages of PROTACS, the biological mechanisms behind their function, and the proximity binding assay for drug-protein and protein-protein interactions.