NMR in integrated biophysical drug discovery for RAS: past, present, and future
Marshall C, KleinJan F, Gebregiworgis T, Lee K, Fang Z, Eves B, Liu N, Gasmi-Seabrook G, Enomoto M, Ikura M. NMR in integrated biophysical drug discovery for RAS: past, present, and future. Journal Of Biomolecular NMR 2020, 74: 531-554. PMID: 32804298, DOI: 10.1007/s10858-020-00338-6.Peer-Reviewed Original ResearchMeSH KeywordsCyclic Nucleotide Phosphodiesterases, Type 6Drug DiscoveryGuanine Nucleotide Exchange FactorsHumansMembrane ProteinsMutationNuclear Magnetic Resonance, BiomolecularPrenylationProtein BindingProto-Oncogene Proteins p21(ras)Signal TransductionSmall Molecule LibrariesConceptsGTPase domainProper membrane localizationMultiple signaling cascadesOncogenic Ras mutationsKey downstream effectorDrug discoveryGTPase cycleMembrane localizationRAS proteinsGTP hydrolysisConformational selectionRAS signalingDownstream effectorsSignaling cascadesLipid modificationG12C mutantUpstream regulatorBiophysical approachesSmall proteinsRAS oncogenesDruggable pocketHuman cancersCell growthCovalent inhibitorsPeptidyl inhibitors