Authors: Paul Bamborough, Chun-wa Chung, Emmanuel Hubert Demont, Rebecca C. Furze, Andrew J. Bannister, Ka Hing Che, Hawa Diallo, Clement Douault, Paola Grandi, Tony Kouzarides, Anne-Marie Michon, Darren Jason Mitchell, Rab K. Prinjha, Christina Rau, Samuel Robson, Robert J. Sheppard, Richard J. Upton, Robert J. Watson
Venue: Angewandte Chemie International Edition
Type: Publication
Abstract: AbstractATAD2 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.
Topics: 
Combinatorial chemistry
Stereochemistry
Loading (it may take a couple of seconds)...
Loading (it may take a couple of seconds)...