5LJ1

N-TERMINAL BROMODOMAIN OF HUMAN BRD4 WITH 8-(((3R,4R,5S)-3-((4,4-difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one

Summary for 5LJ1

• Entry DOI: 10.2210/pdb5lj1/pdb
• Descriptor: Bromodomain-containing protein 4, 1,2-ETHANEDIOL, 8-(((3R,4R,5S)-3-((4,4-difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one, ... (4 entities in total)
• Functional Keywords: inhibitor, histone, epigenetic reader, bromodomain, brd4, bromodomain containing protein 4, antagonist, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15689.05

Authors

Chung, C.,Bamborough, P.,Demont, E. (deposition date: 2016-07-17, release date: 2016-08-31, Last modification date: 2024-05-08)

Primary citation

Bamborough, P.,Chung, C.W.,Demont, E.H.,Furze, R.C.,Bannister, A.J.,Che, K.H.,Diallo, H.,Douault, C.,Grandi, P.,Kouzarides, T.,Michon, A.M.,Mitchell, D.J.,Prinjha, R.K.,Rau, C.,Robson, S.,Sheppard, R.J.,Upton, R.,Watson, R.J.
A Chemical Probe for the ATAD2 Bromodomain.
Angew.Chem.Int.Ed.Engl., 55:11382-11386, 2016

PubMed Abstract: ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

PubMed: 27530368
DOI: 10.1002/anie.201603928

Experimental method

X-RAY DIFFRACTION (1.9 Å)