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 A. 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; Apirat Chaikuad; Laura Díaz-Sáez; James M. Bennett; Oleg Fedorov; Kilian V. M. Huber; Jan Huebner; Hilmar Weinmann; Ingo V Hartung; Matyas Gorjanacz
ACS Chem. Biol., 2017, 12, 11, 2730-2736
https://doi.org/10.1021/acschembio.7b00708

Abstract

ATAD2 (ANCCA) is an epigenetic regulator and transcriptional co-factor, whose over-expression 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 chemical probe to explore ATAD2 biology