Keith Graham, Philip Lienau, Benjamin Bader, Stefan Prechtl, Jan Naujoks, Ralf Lesche, Joerg Weiske, Julia Kuehnlenz, Krzysztof Brzezinka, Lisette Potze, Francesca Zanconato, Barbara Nicke, Anna Montebaur, Wilhelm Bone, Sven Golfier, Stefan Kaulfuss, Charlotte Kopitz, Sabine Pilari, Holger Steuber, Sikander Hayat, Atanas Kamburov, Andreas Steffen, Andreas Schlicker, Philipp Buchgraber, Nico Braeuer, Nuria Aiguabella Font, Tobias Heinrich, Lara Kuhnke, Katrin Nowak-Reppel, Carlo Stresemann, Patrick Steigemann, Annette O Walter, Simona Blotta, Matthias Ocker, Ashley Lakner, Franz von Nussbaum, Dominik Mumberg, Knut Eis, Stefano Piccolo, Martin Lange
This study describes the identification and target deconvolution of small molecule inhibitors of oncogenic Yes-associated protein (YAP1)/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution studies identified the geranylgeranyltransferase-I (GGTase-I) complex as the direct target of YAP1/TAZ pathway inhibitors. The small molecule inhibitors block the activation of Rho-GTPases, leading to subsequent inactivation of YAP1/TAZ and inhibition of cancer cell proliferation in vitro...
March 19, 2024: Cell Chemical Biology