2. Academic Validation
  3. Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B

Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B

  • J Med Chem. 2015 Mar 12;58(5):2553-9. doi: 10.1021/jm501963e.
Ludovic Drouin 1,  Sally McGrath,  Lewis R Vidler,  Apirat Chaikuad,  Octovia Monteiro,  Cynthia Tallant,  Martin Philpott,  Catherine Rogers,  Oleg Fedorov,  Manjuan Liu,  Wasim Akhtar,  Angela Hayes,  Florence Raynaud,  Susanne Müller,  Stefan Knapp,  Swen Hoelder
Affiliations

Affiliation

  • 1 The Institute of Cancer Research, Division of Cancer Therapeutics, Cancer Research UK Cancer Therapeutics Unit , 15 Cotswold Road, Sutton, London SM2 5NG, U.K.
PMID: 25719566 DOI: 10.1021/jm501963e
Abstract

The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 (BAZ2-ICR) of the BAZ2A/B bromodomains through rapid optimization of a weakly potent starting point. A key feature of the presented inhibitors is an intramolecular aromatic stacking interaction that efficiently occupies the shallow bromodomain pockets. 13 represents an excellent chemical probe for functional studies of the BAZ2 bromodomains in vitro and in vivo.

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