Abstract

Targeted protein degradation using bifunctional small molecules known as Protein-Targeting Chimeras (PROTACs) is emerging as a novel therapeutic modality. PROTACs redirect the cellular protein quality control machinery to target specific proteins for highly selective degradation and removal from the cell. This is achieved through the binding of one end of the bifunctional molecule to a drug target, the target protein of interest, while the other end simultaneously binds to a cellular ubiquitin E3 ligase. The resultant ternary complex then allows ubiquitination and subsequent degradation of the protein target by the ubiquitin proteasome system. The removal of a disease-causing protein is an attractive therapeutic option. PROTACs possessing efficient cellular degradation of target proteins with functional activity have been described in the literature, with some examples showing in vivo efficacy in disease-relevant models. This presentation aims to highlight the potential of PROTACs in drug discovery with a focus on their pharmacological properties