A Chemical Probe for the ATAD2 Bromodomain

Abstract

ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

Publication
Angew Chem. Int. Ed. Engl. 2016 Sep 12;55(38):11382-6
comments powered by Disqus