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Updated: Oct 16, 2025

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes
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Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

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Covalent PROTACs: the best of both worlds?

Neil P Grimster1

  • 1Oncology R&D, AstraZeneca Waltham USA neil.grimster@astrazeneca.com.

RSC Medicinal Chemistry
|October 21, 2021
PubMed

Insights

Covalent proteolysis targeting chimeras (PROTACs) merge targeted covalent inhibitors (TCIs) with PROTACs. This emerging field shows promise for expanding the druggable proteome, offering new therapeutic strategies.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Covalent PROTACs integrate targeted covalent inhibitors (TCIs) and proteolysis targeting chimeras (PROTACs).
  • This novel approach aims to leverage the strengths of both TCIs and PROTACs for enhanced therapeutic outcomes.

Discussion:

  • Exploration of early findings in covalent PROTAC research.
  • Analysis of the potential advantages, such as prolonged target engagement and unique degradation profiles.
  • Consideration of the disadvantages, including potential off-target toxicities and challenges in drug design.

Key Insights:

  • Covalent PROTACs represent a nascent but promising area in drug discovery.
  • The combination offers potential for overcoming resistance mechanisms and targeting challenging proteins.
  • Early data suggests significant potential for expanding the druggable proteome.

Outlook:

  • Future development of covalent PROTACs could lead to novel therapeutics.
  • Further research is needed to fully understand and mitigate potential risks.
  • This approach may redefine strategies for protein degradation-based therapies.

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