5A5P

Crystal structure of human ATAD2 bromodomain in complex with 8-2-(dimethylamino)ethylamino-3-methyl-1,2-dihydroquinolin-2-one

Summary for 5A5P

• Entry DOI: 10.2210/pdb5a5p/pdb
• Related: 5A5N 5A5O 5A5Q 5A5R 5A5S
• Descriptor: ATPASE FAMILY AAA DOMAIN-CONTAINING PROTEIN 2, 1,2-ETHANEDIOL, 8-{[2-(dimethylamino)ethyl]amino}-3-methyl-1,2-dihydroquinolin-2-one, ... (5 entities in total)
• Functional Keywords: hydrolase, inhibitor, atad2, bromodomain, epigenetics, atpase family aaa domain-containing protein 2
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus : Q6PL18
• Total number of polymer chains: 1
• Total formula weight: 15919.03

Authors

Chung, C.,Bamborough, P.,Demont, E. (deposition date: 2015-06-20, release date: 2015-07-22, Last modification date: 2024-05-08)

Primary citation

Demont, E.H.,Chung, C.,Furze, R.C.,Grandi, P.,Michon, A.,Wellaway, C.,Barrett, N.,Bridges, A.M.,Craggs, P.D.,Diallo, H.,Dixon, D.P.,Douault, C.,Emmons, A.J.,Jones, E.J.,Karamshi, B.V.,Locke, K.,Mitchell, D.J.,Mouzon, B.H.,Prinjha, R.K.,Roberts, A.D.,Sheppard, R.J.,Watson, R.J.,Bamborough, P.
Fragment-Based Discovery of Low-Micromolar Atad2 Bromodomain Inhibitors.
J.Med.Chem., 58:5649-, 2015

PubMed Abstract: Overexpression of ATAD2 (ATPase family, AAA domain containing 2) has been linked to disease severity and progression in a wide range of cancers, and is implicated in the regulation of several drivers of cancer growth. Little is known of the dependence of these effects upon the ATAD2 bromodomain, which has been categorized as among the least tractable of its class. The absence of any potent, selective inhibitors limits clear understanding of the therapeutic potential of the bromodomain. Here, we describe the discovery of a hit from a fragment-based targeted array. Optimization of this produced the first known micromolar inhibitors of the ATAD2 bromodomain.

PubMed: 26155854
DOI: 10.1021/ACS.JMEDCHEM.5B00772

Experimental method

X-RAY DIFFRACTION (2.03 Å)