Kang, C., Xu, W., Song, H., & Hong, W. (2026). Illuminating Clinical TEAD Inhibitors Through Structural Biology. Journal of Medicinal Chemistry, 69(8), 8647–8649. https://doi.org/10.1021/acs.jmedchem.6c01021
Abstract:
The Hippo signaling pathway is a key regulator of cell proliferation, tissue homeostasis, and organ size. Dysregulation of this pathway is strongly associated with tumorigenesis, primarily through aberrant activity of the YAP-TEAD transcriptional complex. Structural studies of TEAD proteins have provided critical insights that enable the rational design of inhibitors, while also revealing previously unrecognized functional mechanisms. Guided by these structural insights, several small-molecule inhibitors have been developed, including compounds that disrupt YAP-TEAD interactions or target the palmitate-binding pocket of TEAD, some of which have advanced into clinical trials. Collectively, these advances highlight the pivotal role of structural biology in informing drug discovery and provide a strong foundation for the continued development of TEAD-targeted small molecule therapeutics.
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Publisher Copyright
Funding Info:
This research is supported by core funding from: Experimental Drug Development Centre (EDDC)
Grant Reference no. : Core