Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation

Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation

Looking for fragments: A fragment‐based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K‐Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment‐derived hits bind to the guanosine diphosphate–K‐Ras complex (see...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Angewandte Chemie International Edition 2012-06, Vol.51 (25), p.6140-6143
Hauptverfasser: Sun, Qi, Burke, Jason P., Phan, Jason, Burns, Michael C., Olejniczak, Edward T., Waterson, Alex G., Lee, Taekyu, Rossanese, Olivia W., Fesik, Stephen W.
Format: Artikel
Sprache:eng
Schlagworte:
Activation
Crystallography, X-Ray
Exchange
fragment-based screening
Fragmentation
Genes, ras - drug effects
GTPases
Guanosines
K-Ras inhibitors
ligand design
Ligands
Molecular Structure
NMR spectroscopy
Nucleotides
Screens
Small Molecule Libraries - chemistry
Small Molecule Libraries - pharmacology
Son of Sevenless Proteins - antagonists & inhibitors
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Looking for fragments: A fragment‐based screen using NMR spectroscopy was applied to discover ligands that bind to the GTPase K‐Ras and modulate the activity of the nucleotide exchange factor Sos. Structural data on how these fragment‐derived hits bind to the guanosine diphosphate–K‐Ras complex (see picture) provides a starting point for the future discovery of drugs that target K‐Ras activation and signaling.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201201358