Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 116; no. 7; pp. 2545 - 2550
• Main Authors: Cruz-Migoni, Abimael, Canning, Peter, Quevedo, Camilo E., Bataille, Carole J. R., Bery, Nicolas, Miller, Ami, Russell, Angela J., Phillips, Simon E. V., Carr, Stephen B., Rabbitts, Terence H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 12.02.2019
• Subjects: Anchoring; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binders; Binding; Biological Sciences; Crystallization; Crystallography, X-Ray; Crystals; Drug Development; Inhibitors; Intracellular; Molecular Structure; Oncogene Protein p21(ras) - antagonists & inhibitors; Oncogene Protein p21(ras) - metabolism; Organic chemistry; Protein Binding; Protein interaction; Proteins; Ras protein; Surface Plasmon Resonance; cancer; antibody; RAS; drugs; intracellular antibody

The RAS gene family is frequently mutated in human cancers, and the quest for compounds that bind to mutant RAS remains a major goal, as it also does for inhibitors of protein–protein interactions. We have refined crystallization conditions for KRAS169 Q61H-yielding crystals suitable for soaking wit...