PROTAC Degraders

Proteolysis-targeting chimeras (PROTACs) are an emerging modality in targeted protein degradation and represent a key class of drugs that may yield significant benefit in the treatment of a wide range of diseases. In recent years, the field has witnessed a significant rise not only in the number of PROTAC molecules being developed and that have reached clinical settings but also in technologies and applications of degraders and beyond. This chapter covers some of the recent advances in the PROTAC space, from novel E3 ligases beyond the most-commonly used CRBN and VHL that have been hijacked, to next-generation degraders such as trivalent PROTACs and covalent PROTACs. We also highlight some of the emerging drug-resistance mechanisms that have been described particularly for VHL and CRBN-recruiting degraders.