Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors

ATAD2
is a bromodomain-containing protein whose overexpression is linked
to poor outcomes in a number of different cancer types. To date, no
potent and selective inhibitors of the bromodomain have been reported.
This article describes the structure-based optimization of a series
of naphthyridones from micromolar leads with no selectivity over the
BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold
BET selectivity.