Frontiers in Chemical Biology

This lecture explores the concept of the druggable proteome, focusing on the human genome and the number of potential drug targets. It discusses the occupancy-driven paradigm in drug development, the PROTACS strategy, and the process of ubiquitin attachment to proteins. The lecture also covers the use of phthalimide conjugation for target protein degradation, screening assays like ALPHA-Screen, and the application of PROTACs in living cells. Additionally, it delves into the effects of dBET1 at the proteome level, expression proteomics with isobaric tags, and in vivo activity testing. The audience will gain insights into the design of PROTACS, the advantages and disadvantages of this drug development strategy, the biological mechanisms behind PROTACs, and the proximity binding assay for drug-protein interactions.