GNE-7883 is a potent and allosteric small-molecule inhibitor of pan-TEAD, that allosterically blocks the interactions between YAP/TAZ and all human TEAD paralogs through binding to the TEAD lipid pocket. It effectively reduces chromatin accessibility at TEAD motifs, suppresses cell proliferation in a variety of cell line models and achieves strong antitumor efficacy in vivo. Furthermore, it effectively overcomes KRAS G12C inhibitor resistance.