2. Academic Validation
  3. Structure-based development of PDEδ inhibitors

Structure-based development of PDEδ inhibitors

  • Biol Chem. 2017 May 1;398(5-6):535-545. doi: 10.1515/hsz-2016-0272.
Pablo Martín-Gago 1,  Eyad Kalawy Fansa 2,  Alfred Wittinghofer 2,  Herbert Waldmann 1
Affiliations

Affiliations

  • 1 Department of Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, D-44227 Dortmund.
  • 2 Structural Biology Group, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, D-44227 Dortmund.
PMID: 27935847 DOI: 10.1515/hsz-2016-0272
Abstract

The prenyl binding protein PDEδ enhances the diffusion of farnesylated Ras proteins in the cytosol, ultimately affecting their correct localization and signaling. This has turned PDEδ into a promising target to prevent oncogenic KRas signaling. In this review we summarize and describe the structure-guided-development of the three different PDEδ inhibitor chemotypes that have been documented so far. We also compare both their potency for binding to the PDEδ pocket and their in vivo efficiency in suppressing oncogenic KRas signaling, as a result of the inhibition of the PDEδ/KRas interaction.

Keywords

KRas; PDEδ; small molecules; structure-based design; structure-property-relationships.

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