Casey J Moure, Brandon Vara, Mangeng M Cheng, Christopher Sondey, Eric Muise, Eunsil Park, Julia Eulalia Vela Ramirez, Dan Su, Shanti D'Souza, Qingyun Yan, Charles S Yeung, Minjia Zhang, My Sam Mansueto, Doug Linn, Mark Buchanan, Robert Foti, Erin DiMauro, Brian Long, Vladimir Simov, Evan R Barry
Many tumor types harbor alterations in the Hippo pathway, including mesothelioma, where a high percentage of cases are considered YAP1/TEAD dependent. Identification of autopalmitoylation sites in the hydrophobic palmitate pocket of TEADs, which may be necessary for YAP1 protein interactions, has enabled modern drug discovery platforms to generate compounds that allosterically inhibit YAP1/TEAD complex formation and transcriptional activity. We report the discovery and characterization of a novel YAP1/TEAD inhibitor MRK-A from an aryl ether chemical series demonstrating potent and specific inhibition of YAP1/TEAD activity...
May 1, 2024: Molecular Cancer Therapeutics