K975

K975 is a potent, selective, and orally bioavailable small molecule inhibitor of the Transcriptional Enhancer Associate Domain (TEAD) transcription factors, which are the primary nuclear effectors of the Hippo signaling pathway. Developed by Kyowa Kirin, K975 acts by covalently binding to a highly conserved cysteine residue within the palmitate-binding pocket of TEAD proteins (TEAD1, TEAD2, TEAD3, and TEAD4). This binding disrupts the interaction between TEAD and its transcriptional co-activators, Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), thereby suppressing the expression of genes associated with cell proliferation, survival, and epithelial-mesenchymal transition (EMT). Preclinical research has demonstrated that K975 can inhibit the growth of YAP/TAZ-dependent tumors, such as malignant mesothelioma and pancreatic ductal adenocarcinoma (PDAC), and may help overcome chemoresistance and metabolic reprogramming in these cancers.

Other names

TEAD inhibitor K975