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Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

Author

Listed:
  • Gunther Zimmermann

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany)

  • Björn Papke

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany)

  • Shehab Ismail

    (Structural Biology Group, Max Planck Institute for Molecular Physiology, D-44227 Dortmund, Germany)

  • Nachiket Vartak

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany)

  • Anchal Chandra

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany)

  • Maike Hoffmann

    (Ruhr-University Bochum, D-44801 Bochum, Germany)

  • Stephan A. Hahn

    (Ruhr-University Bochum, D-44801 Bochum, Germany)

  • Gemma Triola

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany)

  • Alfred Wittinghofer

    (Structural Biology Group, Max Planck Institute for Molecular Physiology, D-44227 Dortmund, Germany)

  • Philippe I. H. Bastiaens

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany
    Chemical Biology, Faculty of Chemistry, TU Dortmund, D-44227 Dortmund, Germany)

  • Herbert Waldmann

    (Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany
    Chemical Biology, Faculty of Chemistry, TU Dortmund, D-44227 Dortmund, Germany)

Abstract

KRAS is one of the most frequently mutated oncogenes and a major target in anticancer drug discovery, but small molecule modulators that work in the clinic have been elusive; here a new approach to target KRAS is described, based on interfering with its binding to the prenyl-binding protein PDEδ.

Suggested Citation

  • Gunther Zimmermann & Björn Papke & Shehab Ismail & Nachiket Vartak & Anchal Chandra & Maike Hoffmann & Stephan A. Hahn & Gemma Triola & Alfred Wittinghofer & Philippe I. H. Bastiaens & Herbert Waldman, 2013. "Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling," Nature, Nature, vol. 497(7451), pages 638-642, May.
    • Handle: RePEc:nat:nature:v:497:y:2013:i:7451:d:10.1038_nature12205
    DOI: 10.1038/nature12205
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