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Publication - Dr Richard Sessions

    Anti-proliferative and anti-migratory effects of a novel YAP-TEAD interaction inhibitor identified using in silico molecular docking

    Citation

    Smith, S, Sessions, R, Shoemark, D, Williams, C, Ebrahimighaei, R, McNeill, M, Crump, M, McKay, TR, Harris, G, Newby, A & Bond, M, 2019, ‘Anti-proliferative and anti-migratory effects of a novel YAP-TEAD interaction inhibitor identified using in silico molecular docking’. Journal of Medicinal Chemistry, vol 62., pp. 1291-1305

    Abstract

    The Hippo pathway is an important regulator of cell growth, proliferation and migration. TEAD transcription factors, which lie at the core of the Hippo pathway, are essential for regulation of organ growth and wound repair. Dysregulation of TEAD and its regulatory co-factor YAP have been implicated in numerous human cancers and hyper-proliferative pathological processes. Hence the YAP-TEAD complex is a promising therapeutic target. Here we use in silico molecular docking using BUDE (Bristol University Docking Engine) to screen a library of more than eight million drug-like molecules for novel disrupters of the YAP-TEAD interaction. We report the identification of a novel compound (CPD3.1) with the ability to disrupt YAP-TEAD protein-protein interaction, inhibit TEAD activity and inhibit cell proliferation and cell migration. The YAP-TEAD complex is a viable drug target and CPD3.1 is a lead compound for development of more potent TEAD inhibitors for treating cancer and other hyper-proliferative pathologies.

    Full details in the University publications repository