5A82

Crystal structure of human ATAD2 bromodomain in complex with 4-(3R,4R) -4-(3-methyl-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl)aminopiperidin-3- yloxymethyl)-1-thiane-1,1-dione

Summary for 5A82

• Entry DOI: 10.2210/pdb5a82/pdb
• Related: 5A81 5A83 5A85
• Descriptor: ATPASE FAMILY AAA DOMAIN-CONTAINING PROTEIN 2, 1,2-ETHANEDIOL, 8-[[(3R,4R)-3-[[1,1-bis(oxidanylidene)thian-4-yl]methoxy]piperidin-4-yl]amino]-3-methyl-1H-1,7-naphthyridin-2-one, ... (5 entities in total)
• Functional Keywords: inhibitor, atad2, bromodomain, epigenetics, atpase family aaa domain-containing protein 2
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 16156.31

Authors

Chung, C.,Bamborough, P.,Demont, E. (deposition date: 2015-07-11, release date: 2015-08-12, Last modification date: 2024-05-08)

Primary citation

Bamborough, P.,Chung, C.,Furze, R.C.,Grandi, P.,Michon, A.,Sheppard, R.J.,Barnett, H.,Diallo, H.,Dixon, D.P.,Douault, C.,Jones, E.J.,Karamshi, B.,Mitchell, D.J.,Prinjha, R.K.,Rau, C.,Watson, R.J.,Werner, T.,Demont, E.H.
Structure-Based Optimization of Naphthyridones Into Potent Atad2 Bromodomain Inhibitors.
J.Med.Chem., 58:6151-, 2015

PubMed Abstract: ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.

PubMed: 26230603
DOI: 10.1021/ACS.JMEDCHEM.5B00773

Experimental method

X-RAY DIFFRACTION (1.86 Å)