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

Gunther Zimmermann, Björn Papke, Shehab Ismail, Nachiket Vartak, Anchal Chandra, Maike Hoffmann, Stephan A. Hahn, Gemma Triola, Alfred Wittinghofer (), Philippe I. H. Bastiaens () and Herbert Waldmann ()
Additional contact information
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
Herbert Waldmann: Max Planck Institute of Molecular Physiology, D-44227 Dortmund, Germany

Nature, 2013, vol. 497, issue 7451, 638-642

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.

Date: 2013
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DOI: 10.1038/nature12205

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