AZ4331

AZ4331 is a potent and selective pan-TEAD autopalmitoylation inhibitor developed by AstraZeneca for the treatment of Hippo-pathway altered cancers. It functions by covalently binding to a conserved cysteine residue within the TEAD1-4 transcription factors, thereby disrupting their post-translational palmitoylation. This inhibition prevents the formation of the oncogenic YAP/TAZ-TEAD complex, leading to reduced expression of TEAD-dependent genes involved in cell survival, proliferation, and drug resistance. In preclinical studies, AZ4331 has demonstrated significant anti-tumor activity in xenograft models of mesothelioma, head and neck squamous cell carcinoma, and other cancers characterized by NF2 mutations, LATS1/2 loss, or YAP1 amplification.