TED-347

TED-347 is a selective, small molecule covalent inhibitor of the Transcriptional Enhancer Associate Domain (TEAD) transcription factors, which are key effectors of the Hippo signaling pathway. It functions by binding to a conserved cysteine residue within the TEAD palmitoylation pocket (e.g., Cys-359 in TEAD1), thereby allosterically disrupting the interaction between TEAD and its transcriptional co-activator, Yes-associated protein 1 (YAP1). This disruption prevents the formation of the YAP1/TEAD transcriptional complex, leading to the downregulation of oncogenic genes involved in cell proliferation, survival, and epithelial-mesenchymal transition (EMT). Recent research has also identified TED-347's role in modulating the crosstalk between the YAP1/TEAD and NF-kappa B pathways, particularly in prostate cancer models where it suppresses tumor growth, induces apoptosis, and reduces the expression of cancer stem cell markers such as CD44 and CXCR4.