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

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. In...

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Bibliographic Details
Published in:Nature (London) 2013-05, Vol.497 (7451), p.638-642
Main Authors: Zimmermann, Gunther, Papke, Björn, Ismail, Shehab, Vartak, Nachiket, Chandra, Anchal, Hoffmann, Maike, Hahn, Stephan A., Triola, Gemma, Wittinghofer, Alfred, Bastiaens, Philippe I. H., Waldmann, Herbert
Format: Article
Language:English
Subjects:
631/67/395
631/80/86/2368
631/92/613
Adenocarcinoma - drug therapy
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Animals
Benzimidazoles - chemistry
Benzimidazoles - metabolism
Benzimidazoles - pharmacology
Benzimidazoles - therapeutic use
Binding Sites
Carcinoma, Pancreatic Ductal - drug therapy
Carcinoma, Pancreatic Ductal - genetics
Carcinoma, Pancreatic Ductal - metabolism
Cell Line
Cell Line, Tumor
Cell Proliferation - drug effects
Cell research
Crystals
Cyclic Nucleotide Phosphodiesterases, Type 6 - antagonists & inhibitors
Cyclic Nucleotide Phosphodiesterases, Type 6 - chemistry
Cyclic Nucleotide Phosphodiesterases, Type 6 - metabolism
Dogs
Fluorescence microscopy
Humanities and Social Sciences
Humans
Hydrogen Bonding
letter
MAP Kinase Signaling System - drug effects
Mice
Mice, Nude
Mitogen-Activated Protein Kinases - metabolism
Models, Molecular
Molecular Conformation
multidisciplinary
Neoplasm Transplantation
Oncogene Protein p21(ras) - antagonists & inhibitors
Oncogene Protein p21(ras) - genetics
Oncogene Protein p21(ras) - metabolism
Peptides
Properties
Protein Binding - drug effects
Ras genes
Science
Signal Transduction - drug effects
Structure
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