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A chemical probe for the ATAD2 bromodomain

Research output: Contribution to journalArticlepeer-review

  • Paul Bamborough
  • Chun-wa Chung
  • Emmanuel H. Demont
  • Rebecca C. Furze
  • Andrew J. Bannister
  • Ka Hing Che
  • Hawa Diallo
  • Clement Douault
  • Paola Grandi
  • Tony Kouzarides
  • Anne-Marie Michon
  • Darren J. Mitchell
  • Rab K. Prinjha
  • Christina Rau
  • Dr Samuel Robson
  • Robert J. Sheppard
  • Richard Upton
  • Robert J. Watson
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.
Original languageEnglish
Pages (from-to)11382-11386
Number of pages5
JournalAngewandte Chemie International Edition
Volume55
Issue number38
Early online date17 Aug 2016
DOIs
Publication statusPublished - 12 Sep 2016
Externally publishedYes

Documents

  • A Chemical Probe

    Rights statement: This is the peer reviewed version of the following article: P. Bamborough, C.-w. Chung, E. H. Demont, R. C. Furze, A. J. Bannister, K. H. Che, H. Diallo, C. Douault, P. Grandi, T. Kouzarides, A.-M. Michon, D. J. Mitchell, R. K. Prinjha, C. Rau, S. Robson, R. J. Sheppard, R. Upton, R. J. Watson, Angew. Chem. Int. Ed. 2016, 55, 11382., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/anie.201603928/full. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

    Accepted author manuscript (Post-print), 544 KB, PDF document

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