A Chemical Probe for the ATAD2 Bromodomain. (17th August 2016)

• Record Type: Journal Article
• Authors: Bamborough, Paul; Chung, Chun‐wa; Demont, Emmanuel H.; Furze, Rebecca C.; Bannister, Andrew J.; Che, Ka Hing; Diallo, Hawa; Douault, Clement; Grandi, Paola; Kouzarides, Tony; Michon, Anne‐Marie; Mitchell, Darren J.; Prinjha, Rab K.; Rau, Christina; Robson, Samuel; Sheppard, Robert J.; Upton, Richard; Watson, Robert J.
• Is Part Of: Angewandte Chemie. Volume 128:Number 38(2016)
• Page Start: 11554
• Page End: 11558
• Publication Date: 2016-08-17
• Subjects: Bioisostere -- Epigenetik -- Fluor -- Konformationsanalyse -- Medizinische Chemie; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201603928
• Languages: English
• ISSNs: 0044-8249

Abstract

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.