2. Academic Validation
  3. GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins

GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins

  • J Med Chem. 2020 Sep 10;63(17):9045-9069. doi: 10.1021/acs.jmedchem.0c00614.
Robert J Watson,  Paul Bamborough,  Heather Barnett,  Chun-Wa Chung,  Rob Davis,  Laurie Gordon,  Paola Grandi 1,  Massimo Petretich 1,  Alex Phillipou,  Rab K Prinjha,  Inmaculada Rioja,  Peter Soden,  Thilo Werner 1,  Emmanuel H Demont
Affiliations

Affiliation

  • 1 Molecular Discovery Research, GlaxoSmithKline, Cellzome GmbH, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
PMID: 32691589 DOI: 10.1021/acs.jmedchem.0c00614
Abstract

Pan-bromodomain and extra terminal (BET) inhibitors interact equipotently with all eight bromodomains of the BET family of proteins. They have shown profound efficacy in vitro and in vivo in oncology and immunomodulatory models, and a number of them are currently in clinical trials where significant safety signals have been reported. It is therefore important to understand the functional contribution of each bromodomain to assess the opportunity to tease apart efficacy and toxicity. This article discloses the in vitro and cellular activity profiles of GSK789, a potent, cell-permeable, and highly selective inhibitor of the first bromodomains of the BET family.

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