Isoform-selective ATAD2 chemical probe with novel chemical structure and unusual mode of action.

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.