PROTACs: Opportunities and Challenges Ahead in the Field of Drug Discovery

Proteolysis Targeting Chimeras (PROTACs) are alternatives to traditional small molecule-based drug discovery techniques that focus on direct regulation of protein activity. Targeted protein degradation in cells by heterobifunctional small molecules has emerged as one of the most promising technologies for modulating a protein of interest (POI). PROTACs connect three chemical elements: POI ligand to an E3 ubiquitin ligase (E3) recruiting ligand with an optimal linker for conjugating these two ligands.1 PROTACs cause degradation via the ubiquitinproteasome system (UPS) through proximityinduced ubiquitination of the POI. PROTACs induce target protein degradation at low exposures due to their catalytic mode of action thus making them an attractive platform for cancer therapy and other diseases.  Read more....