6Z7M

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 (3R,4R)-N-cyclohexyl-4-((3-methyl-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl)amino)piperidine-3-carboxamide

This is a non-PDB format compatible entry.

Summary for 6Z7M

• Entry DOI: 10.2210/pdb6z7m/pdb
• Related: 6Z7L
• Descriptor: Bromodomain-containing protein 4, (3R,4R)-N-cyclohexyl-4-((3-methyl-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl)amino)piperidine-3-carboxamide (3 entities in total)
• Functional Keywords: inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 15482.87

Authors

Chung, C. (deposition date: 2020-05-31, release date: 2020-07-29, Last modification date: 2024-05-01)

Primary citation

Watson, R.J.,Bamborough, P.,Barnett, H.,Chung, C.W.,Davis, R.,Gordon, L.,Grandi, P.,Petretich, M.,Phillipou, A.,Prinjha, R.K.,Rioja, I.,Soden, P.,Werner, T.,Demont, E.H.
GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins.
J.Med.Chem., 63:9045-9069, 2020

PubMed 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.

PubMed: 32691589
DOI: 10.1021/acs.jmedchem.0c00614

Experimental method

X-RAY DIFFRACTION (1.26 Å)