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- Title
A Chemical Probe for the ATAD2 Bromodomain.
- 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.
- 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.
- Subjects
BROMODOMAIN-containing proteins; NUCLEAR proteins; PERMEABILITY; PIPERIDINE; HETEROCYCLIC compounds
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 38, p11554
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201603928