Subsequent structure-based design to engage a side pocket resulted in development of a more potent covalent TEAD inhibitor MYF-03–69, which inhibits the palmitoylation process of all four TEAD paralogs in vitro by occupying the Y-shaped pocket, disassociates the endogenous YAP-TEAD complex, downregulates YAP-dependent target gene expression, and preferentially impairs the proliferation of mesothelioma cells that exhibit defects in Hippo signaling. Here, YAP1 is linked to mesothelioma.