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GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain.

ABSTRACT: 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 micromolar 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.

SUBMITTER: Bamborough P

PROVIDER: S-EPMC4904261 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain.

Bamborough Paul P Barnett Heather A HA Becher Isabelle I Bird Mark J MJ Chung Chun-Wa CW Craggs Peter D PD Demont Emmanuel H EH Diallo Hawa H Fallon David J DJ Gordon Laurie J LJ Grandi Paola P Hobbs Clare I CI Hooper-Greenhill Edward E Jones Emma J EJ Law Robert P RP Le Gall Armelle A Lugo David D Michon Anne-Marie AM Mitchell Darren J DJ Prinjha Rab K RK Sheppard Robert J RJ Watson Allan J B AJ Watson Robert J RJ

ACS medicinal chemistry letters 20160509 6

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 micromolar 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. ...[more]

PMID: 27326325

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