1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain

  • ACS Med Chem Lett. 2014 Sep 10;5(11):1190-5. doi: 10.1021/ml5002932.
Emmanuel H Demont  1 ,  Paul Bamborough  1 ,  Chun-Wa Chung  1 ,  Peter D Craggs  1 ,  David Fallon  1 ,  Laurie J Gordon  1 ,  Paola Grandi  2 ,  Clare I Hobbs  1 ,  Jameed Hussain  1 ,  Emma J Jones  1 ,  Armelle Le Gall  1 ,  Anne-Marie Michon  2 ,  Darren J Mitchell  1 ,  Rab K Prinjha  1 ,  Andy D Roberts  3 ,  Robert J Sheppard  1 ,  Robert J Watson  1
Affiliations
  • 1. Epinova Discovery Performance Unit and Molecular Discovery Research, GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
  • 2. Cellzome GmbH, Molecular Discovery Research, GlaxoSmithKline , Meyerhofstrasse 1, 69117 Heidelberg, Germany.
  • 3. DMPK, GlaxoSmithKline , Park Road, Ware SG12 0DP, U.K.
PMID: 25408830 DOI: 10.1021/ml5002932
Abstract

The BRPF (bromodomain and PHD finger-containing) protein family are important scaffolding proteins for assembly of MYST Histone Acetyltransferase complexes. Here, we report the discovery, binding mode, and structure-activity relationship (SAR) of the first potent, selective series of inhibitors of the BRPF1 bromodomain.

Keywords
BRD1; BRPF1; BRPF2; BRPF3; bromodomain; chemical probe; epigenetics; fragment; inhibitor.
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