A Chemical Probe for the ATAD2 Bromodomain
Demont, Emmanuel H
Furze, Rebecca C
Che, Ka Hing
Mitchell, Darren J
Sheppard, Robert J
Watson, Robert J
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Bamborough, P., Chung, C., Demont, E. H., Furze, R. C., Bannister, A., Che, K. H., Diallo, H., et al. (2016). A Chemical Probe for the ATAD2 Bromodomain. Angewandte Chemie, 128 (38), 11554-11558. https://doi.org/10.1002/ange.201603928
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.
A.J.B., K.H.C., S.R. and T.K. acknowledge grants from Wellcome Trust (092096), Cancer Research UK (C6946/A14492, RG17001), and BBSRC (RG69031).
Wellcome Trust (092096/Z/10/Z)
Cancer Research UK (A14492)
External DOI: https://doi.org/10.1002/ange.201603928
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303269