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The TEA/ATSS (TEAD) family of transcription factors are key effectors of the Hippo pathway, exerting their function through interactions with the coactivators YAP and TAZ. Over the past five years, the development of YAP-TEAD disruptors has emerged as a central focus of both academic and industrial efforts aimed at targeting the Hippo pathway for cancer therapy. In this study, the discovery and comprehensive characterization of KG-FP-003, a potent, selective, and durable TEAD degrader is reported. KG-FP-003 exhibits superior activity compared to the lipid-binding pocket (LBP) inhibitor MYF-03-176 and the TEAD-YAP protein-protein interaction (PPI) inhibitor IAG933, efficiently degrading all TEAD isoforms at low nanomolar concentrations in a ubiquitin-proteasome system (UPS)-dependent manner. This degradation translates into more robust and sustained therapeutic responses both in vitro and in vivo. Furthermore, barcoded cell line screening revealed elevated sensitivity in several cancer types, including endometrial carcinoma, glioblastoma, ovarian epithelial tumors, and osteosarcoma. These findings position KG-FP-003 as a compelling lead candidate for TEAD isoform-selective therapies and underscore its potential utility beyond Hippo-dysregulated mesothelioma.