2区 · 生物学
Article
作者: Stöckigt, Detlef ; Clark, Matthew A. ; Gorjánácz, Mátyás ; Badock, Volker ; Hartung, Ingo V. ; Kuropka, Benno ; Weiske, Joerg ; Fernández-Montalván, Amaury E. ; Díaz-Sáez, Laura ; Berger, Markus ; Puetter, Vera ; Holton, Simon J. ; Keefe, Anthony D. ; Fedorov, Oleg ; Zhang, Ying ; Centrella, Paolo A. ; Sigel, Eric A. ; Dumelin, Christoph E. ; Soutter, Holly H. ; Bennett, James M. ; Roche, Didier ; ter Laak, Antonius ; Cuozzo, John W. ; Huber, Kilian V. M. ; Chaikuad, Apirat ; Koo, Seong Joo ; Troast, Dawn M. ; Hübner, Jan ; Rodeschini, Vincent ; Weinmann, Hilmar
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.