Frontiers in PROTACs
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Updated: Nov 8, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
Published on: January 12, 2024
Gregory R Hughes1, Ashley P Dudey2, Andrew M Hemmings3
1School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK; Department of Chemistry, King's College London, SE1 1DB, UK.
Abstract:
Targeting protein-protein interactions (PPI) is a key focus in the development of new and emerging small-molecule therapeutics. Shallow interacting surfaces can render PPI targeting notoriously difficult. This leaves many therapeutically captivating targets 'undruggable'. Despite these challenges, there has been extraordinary progress circumventing this issue by hijacking the ubiquitin proteasome system (UPS) to target selected substrates for destruction using target-based degradation (TBD) strategies, including bifunctional molecules known as proteolysis-targeting chimeras (PROTACs). In this review, we discuss some of the most recent innovative concepts emerging from PROTAC research and related technologies.
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