The PROTACtable genome

Nat Rev Drug Discov. 2021 Oct;20(10):789-797. doi: 10.1038/s41573-021-00245-x. Epub 2021 Jul 20.


Proteolysis-targeting chimeras (PROTACs) are an emerging drug modality that may offer new opportunities to circumvent some of the limitations associated with traditional small-molecule therapeutics. By analogy with the concept of the 'druggable genome', the question arises as to which potential drug targets might PROTAC-mediated protein degradation be most applicable. Here, we present a systematic approach to the assessment of the PROTAC tractability (PROTACtability) of protein targets using a series of criteria based on data and information from a diverse range of relevant publicly available resources. Our approach could support decision-making on whether or not a particular target may be amenable to modulation using a PROTAC. Using our approach, we identified 1,067 proteins of the human proteome that have not yet been described in the literature as PROTAC targets that offer potential opportunities for future PROTAC-based efforts.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Genome*
  • Humans
  • Research Design
  • Small Molecule Libraries


  • Small Molecule Libraries