GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2)

The
biological function of bromodomains, epigenetic readers of
acetylated lysine residues, remains largely unknown. Herein we report
our efforts to discover a potent and selective inhibitor of the bromodomain
of cat eye syndrome chromosome region candidate 2 (CECR2). Screening
of our internal medicinal chemistry collection led to the identification
of a pyrrolopyridone chemical lead, and subsequent structure-based
drug design led to a potent and selective CECR2 bromodomain inhibitor
(GNE-886) suitable for use as an in vitro tool compound.