PROTACs technology for targeting non-oncoproteins: Advances and perspectives

Abstract

Proteolysis targeting chimeras (PROTACs) have been developed to be an effective technology for targeted protein degradation. Each PROTAC contains three key components: a protein-of-interest (POI) ligand, an E3 ligase ligand, and a linker. These bifunctional molecules can hijack the intracellular inherent ubiquitin-proteasome system to degrade different POIs. With several advantages over other therapeutic strategies, PROTACs have set off a new upsurge of drug discovery in recent years. PRTOACs have been extensively explored worldwide and have excelled not only in cancer diseases but also in cardiovascular diseases, fatty liver disease, immune diseases, neurodegenerative diseases, and viral infections. In this review, we aim to summarize the rapid progress from 2010 to 2021 in PROTACs targeting various non-oncoproteins and elucidate the advantages of PROTACs technology. Finally, the potential challenges of this dynamic field are also discussed.

Keywords: Bifunctional molecules; Drug discovery; Drug resistance; PROTACs; Target protein degradation; Undruggable target.