TM2 TEAD inhibitor, a robust and reversible inhibitor of the TEA domain transcription factor, presents dual inhibitory concentrations (IC50) of 38 nM for TEAD4 auto-palmitoylation and 156 nM for TEAD2 palmitoylation. It effectively blocks the TEAD-YAP association and their transcriptional activities, leading to significant antiproliferative effects in YAP-dependent cancer cell lines, both as a standalone agent and in combination with a MEK inhibitor. Additionally, it impedes YAP-dependent liver organoid growth ex vivo.