Open AccessGSK973 Is an Inhibitor of the Second Bromodomains (BD2s) of the Bromodomain and Extra-Terminal (BET) Family
Author(s) -
Alex Preston,
Sophie Atkinson,
Paul Bamborough,
Chunwa Chung,
Laurie J. Gordon,
Paola Grandi,
James R. Gray,
Lee A. Harrison,
Antonia J. Lewis,
David Lugo,
Cassie Messenger,
Anne-Marie Michon,
Darren J. Mitchell,
Rab K. Prinjha,
Inmaculada Rioja,
Jon T. Seal,
S. Taylor,
Pierre Thesmar,
Ian D. Wall,
Robert J. Watson,
James M. Woolven,
Emmanuel H. Demont
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00247
Subject(s) - bromodomain , in vivo , bet inhibitor , pharmacology , brd4 , medicine , in vitro , adverse effect , chemistry , computational biology , bioinformatics , biology , biochemistry , genetics , epigenetics , gene
Pan-BET inhibitors have shown profound efficacy in a number of in vivo preclinical models and have entered the clinic in oncology trials where adverse events have been reported. These inhibitors interact equipotently with the eight bromodomains of the BET family of proteins. To better understand the contribution of each domain to their efficacy and to improve from their safety profile, selective inhibitors are required. This Letter discloses the profile of GSK973, a highly selective inhibitor of the second bromodomains of the BET proteins that has undergone extensive preclinical in vitro and in vivo characterization.