The rise and rise of protein degradation: Opportunities and challenges ahead.

The transformational mechanism of action underpinning targeted protein degradation strategies, including proteolysis-targeting chimeras (PROTACs), gives potential for potent in vivo pharmacology and has allowed projects to move rapidly to the clinic. Despite this remarkable progress, there remain many opportunities to improve current, first-generation approaches even further. Our expanding knowledge will allow discovery of new degrading mechanisms with potential to address several limitations of current approaches, including improving scope and efficiency of degradation, improving drug-like properties of degraders, and reducing potential for the emergence of acquired resistance. Here, we discuss potential routes to realize these advances to expand TPD utility even further.

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Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest All authors are employees of Amphista Therapeutics Ltd, a biotechnology company focused on developing new drugs using next generation TPD strategies.