Abstract

Harnessing the ubiquitin-proteasome system for targeted protein degradation has seen an upsurge in interest over recent years in academic, biotech and pharma groups alike. Proteolysis Targeting Chimeras (PROTACs) are bivalent molecules that recruit an E3 ubiquitin ligase and a protein of interest (POI) to induce the degradation of that POI. PROTAC-mediated degradation of a target protein offers a method of advancing our understanding of a biological system orthogonal to techniques such as genetic knockdown or inhibition. As a drug discovery paradigm, this novel modality offers potential advantages over classical small molecule approaches such as a catalytic mode of action, no pre-requisite for functionally active binding sites and opportunities for improved target selectivity. This talk will discuss breakthroughs made by the Ciulli group and others in developing our understanding of how PROTACs work and how the lessons learnt are impacting the burgeoning field of PROTAC drug discovery.