GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain

被引：52

作者：

Bamborough, Paul ^{[4
]}

Barnett, Heather A. ^{[3
]}

Becher, Isabelle ^{[5
,8
]}

Bird, Mark J. ^{[3
]}

Chung, Chun-wa ^{[4
]}

Craggs, Peter D. ^{[4
]}

Demont, Emmanuel H. ^{[1
]}

Diallo, Hawa ^{[1
]}

Fallon, David J. ^{[1
,6
]}

Gordon, Laurie J. ^{[4
]}

Grandi, Paola ^{[5
]}

Hobbs, Clare I. ^{[4
]}

Hooper-Greenhill, Edward ^{[2
]}

Jones, Emma J. ^{[4
]}

Law, Robert P. ^{[1
,6
]}

Le Gall, Armelle ^{[4
]}

Lugo, David ^{[2
]}

Michon, Anne-Marie ^{[5
]}

Mitchell, Darren J. ^{[1
]}

Prinjha, Rab K. ^{[1
]}

Sheppard, Robert J. ^{[1
,7
]}

Watson, Allan J. B. ^{[6
]}

Watson, Robert J. ^{[1
]}

机构：

[1] GlaxoSmithKline, Epinova Discovery Performance Unit, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[2] GlaxoSmithKline, Quantitat Pharmacol Expt Med Unit, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[3] GlaxoSmithKline, Flexible Discovery Unit, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[4] GlaxoSmithKline, Platform Technol & Sci, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England

[5] GlaxoSmithKline, Cellzome GmbH, Meyerhofstr 1, D-69117 Heidelberg, Germany

[6] Univ Strathclyde, Dept Pure & Appl Chem, WestCHEM, Thomas Graham Bldg,295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland

[7] AstraZeneca, Oncol Innovat Med & Early Dev, Cambridge Sci Pk,Milton Rd, Cambridge CB4 OWG, England

[8] European Mol Biol Lab, Genome Biol Unit, Meyerhofstr 1, D-69012 Heidelberg, Germany

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 06期

关键词：

BRPF1; BRPF2; BRD1; BRPF3; BET; bromodomain; epigenetics; chemical probe; inhibitor; HISTONE ACETYLTRANSFERASE; RECOGNITION; DISCOVERY; INSIGHTS; MOZ;

D O I：

10.1021/acsmedchemlett.6b00092

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The BRPF (Bromodomain and PHD Finger-containing) protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. A selective benzimidazolone BRPF1 inhibitor showing micro molar activity in a cellular target engagement assay was recently described. Herein, we report the optimization of this series leading to the identification of a superior BRPF1 inhibitor suitable for in vivo studies.

引用

页码：552 / 557

页数：6

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