Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action
ACS Chemical Biology2017Vol. 12(11), pp. 2730–2736
Citations Over TimeTop 10% of 2017 papers
Amaury E. Fernández‐Montalván, Markus Berger, Benno Kuropka, Seong Joo Koo, Volker Badock, Joerg Weiske, Vera Puetter, Simon J. Holton, Detlef Stöckigt, Antonius ter Laak, Paolo A. Centrella, Matthew Clark, Christoph E. Dumelin, Eric A. Sigel, Holly H. Soutter, Dawn M. Troast, Ying Zhang, John W. Cuozzo, Anthony D. Keefe, Didier Roche, Vincent Rodeschini, A. Chaikuad, L. Diaz Saez, James M. Bennett, Oleg Fedorov, K. Huber, Jan Hübner, Hilmar Weinmann, Ingo V. Hartung, Mátyás Gorjánácz
Abstract
ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically induces ATAD2 bromodomain dimerization and prevents interactions with acetylated histones in vitro, as well as with chromatin in cells. These features qualify BAY-850 as a chemical probe to explore ATAD2 biology.
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