SWTX-143

**SWTX-143** is a novel covalent small molecule inhibitor of the YAP/TAZ-TEAD transcriptional complex, targeting the Hippo signaling pathway dysregulated in multiple cancers. It irreversibly binds to the palmitoylation pocket of all four TEAD isoforms (TEAD1-4), blocking auto-palmitoylation and thereby preventing YAP/TAZ-TEAD interaction and downstream transcriptional output. Developed by **SpringWorks Therapeutics** in collaboration with **Cistim Leuven vzw** and academic partners including **VIB Center for Cancer Biology** and **KU Leuven**, it demonstrates potent antitumor activity in preclinical models, including strong tumor regression in subcutaneous and orthotopic mesothelioma xenografts driven by NF2/LATS2 mutations, as well as selective growth inhibition in NF2-mutant kidney cancer cell lines. SWTX-143 is a tool compound used to validate Hippo pathway targeting, with no reported clinical trials as of late 2023.[1][5][10][11]