1,3-dimethyl benzimidazolones are potent, selective inhibitors of the BRPF1 bromodomain

DOI: 10.1021/ml5002932
PMID: 25408830

Authors: Emmanuel H. Demont (GlaxoSmithKline) , Paul Bamborough (GlaxoSmithKline) , Chun-Wa Chung (GlaxoSmithKline) , Peter D. Craggs (GlaxoSmithKline) , David Fallon (GlaxoSmithKline) , Laurie J. Gordon (GlaxoSmithKline) , Paola Grandi (GlaxoSmithKline) , Clare I. Hobbs (GlaxoSmithKline) , Jameed Hussain (GlaxoSmithKline) , Emma J. Jones (GlaxoSmithKline) , Armelle Le Gall (GlaxoSmithKline) , Anne-Marie Michon (GlaxoSmithKline) , Darren J. Mitchell (GlaxoSmithKline) , Rab K. Prinjha (GlaxoSmithKline) , Andy D. Roberts (GlaxoSmithKline) , Robert J. Sheppard (GlaxoSmithKline) , Robert J. Watson (GlaxoSmithKline)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acs Medicinal Chemistry Letters , VOL 5 (11) , PAGES 1190 - 1195

State: Published (Approved)
Published: November 2014

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.

Journal Keywords: Brpf1; Brpf2; Brd1; Brpf3; Bromodomain; Chemical Probe; Epigenetics; Fragment; Inhibitor

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I03-Macromolecular Crystallography

Added On: 23/11/2015 10:56

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)