A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models

The Hippo pathway regulates the YAP and TAZ transcriptional coactivators, which are often upregulated in human cancers. YAP/TAZ partner with TEAD transcription factors to drive cancer phenotypes. Because mutations in the Hippo pathway genes NF2 and LATS2 lead to YAP/TAZ hyperactivation, mesothelioma is a prime candidate for treatment with YAP/TAZ-TEAD inhibitors. Mesothelioma currently has no good treatment options. The authors developed a new covalent YAP/TAZ-TEAD inhibitor called SWTX-143 that binds all TEAD isoforms and blocks YAP/TAZ-TEAD transcriptional activity. SWTX-143 caused strong tumor regression in mesothelioma mouse models, including a subcutaneous xenograft model and an orthotopic model. <a href="https://medium.com/@axialxyz/a-novel-irreversible-tead-inhibitor-swtx-143-blocks-hippo-pathway-transcriptional-output-and-98a1394e6055">Click Here</a>