2. Academic Validation
  3. 1,3-Dimethyl Benzimidazolones Are Potent, Selective Inhibitors of the BRPF1 Bromodomain

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

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.

Figures
Products