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.

Original languageEnglish
Pages (from-to)2377-2383
Number of pages7
JournalDrug Discovery Today
Issue number10
Early online date17 Apr 2021
Publication statusPublished - Oct 2021


  • Drug discovery
  • Ubiquitin ligases

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