Probing the KRas Switch II Groove by Fluorine NMR Spectroscopy
While there has been recent success in the development of KRas^(G12C) inhibitors, unmet needs for selective inhibitors of KRas^(G12D) and the remaining oncogenic KRas proteins remain. Here, we applied trifluoromethyl-containing ligands of KRas proteins as competitive probe ligands to assay the occupancy of the switch II pocket by ^(19)F NMR spectroscopy. Structure-activity-relationship studies of probe ligands increased the sensitivity of the assay and identified structures that differentially...
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