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Updated: Feb 17, 2026

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
Published on: February 23, 2024
The Keap1-Nrf2 protein-protein interaction: A suitable target for small molecules
Dieter Schmoll1, Christian K Engel1, Heiner Glombik1
1Sanofi R&D, Industriepark Hoechst, D-65926 Frankfurt, Germany.
Abstract:
The transcription factor Nrf2 controls pathways involved in oxidative-stress defense and is a potential pharmacological target for the treatment of chronic diseases. Activators of Nrf2 that have undergone clinical development are reactive molecules that are either associated with safety issues or for which it is unclear if their pharmacological efficacy depends on the activation of Nrf2. Therefore, the clinical validity of Nrf2 activation is not yet proven. The activity of Nrf2 is inhibited by Keap1 via a protein-protein interaction. Its structural characteristics allowed the identification of reversible small-molecule inhibitors of the Keap1-Nrf2 interaction that can hopefully elucidate the therapeutic potential of Nrf2 activation.
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