molecules of the month

Context. “Compound 6” (Novartis) is a first-in-class YAP-TEAD protein-protein inhibitor. The TEAD transcription factor and its coactivator YAP and WWTR1/TAZ of the Hippo pathway are responsible for directly regulating the expression of genes involved in cell proliferation and organ size. Several kinases in the cascade have recently gained attention as potential therapeutic targets for certain cancers. The interaction between YAP and TEAD is important for Hippo signaling, which is dysregulated in some cancers, and disrupting this interaction could be a therapeutic strategy for suppressing Hippo-mediated proliferation. To date, the only published small molecules that attempt to directly target the YAP-TEAD protein-protein interface have shown weak activity, although several have been reported that inhibit TEAD auto-palmitoylation, including one of April 2021’s…