6HDN
Crystal structure of human ATAD2 bromodomain in complex with 3-methyl-8-((8-methyl-8-azabicyclooctan-3-yl)amino)-1,7-naphthyridin-2(1H)-one
Summary for 6HDN
| Entry DOI | 10.2210/pdb6hdn/pdb |
| Descriptor | ATPase family AAA domain-containing protein 2, SULFATE ION, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | inhibitor, atad2, bromodomain, epigenetics, atpase family aaa domain-containing protein 2, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 16164.22 |
| Authors | Chung, C. (deposition date: 2018-08-18, release date: 2018-09-26, Last modification date: 2024-05-15) |
| Primary citation | Bamborough, P.,Chung, C.W.,Furze, R.C.,Grandi, P.,Michon, A.M.,Watson, R.J.,Mitchell, D.J.,Barnett, H.,Prinjha, R.K.,Rau, C.,Sheppard, R.J.,Werner, T.,Demont, E.H. Aiming to Miss a Moving Target: Bromo and Extra Terminal Domain (BET) Selectivity in Constrained ATAD2 Inhibitors. J. Med. Chem., 61:8321-8336, 2018 Cited by PubMed Abstract: ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of its class. In our recent disclosure of the first chemical probe against this bromodomain, GSK8814 (6), we described the use of a conformationally constrained methoxy piperidine to gain selectivity over the BET bromodomains. Here we describe an orthogonal conformational restriction strategy of the piperidine ring to give potent and selective tropane inhibitors and show structural insights into why this was more challenging than expected. Greater understanding of why different rational approaches succeeded or failed should help in the future design of selectivity in the bromodomain family. PubMed: 30226378DOI: 10.1021/acs.jmedchem.8b00862 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.9 Å) |
Structure validation
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