7NQ5
C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH 3-(2-(benzyloxy)phenyl)-5-methyl-1H-1,2,4-triazole
This is a non-PDB format compatible entry.
Summary for 7NQ5
| Entry DOI | 10.2210/pdb7nq5/pdb |
| Descriptor | Bromodomain-containing protein 2, 1,2-ETHANEDIOL, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (5 entities in total) |
| Functional Keywords | inhibitor, histone, epigenetic reader, bromodomain, brd2, bromodomain containing protein 2, antagonist, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14238.41 |
| Authors | Chung, C. (deposition date: 2021-03-01, release date: 2021-03-24, Last modification date: 2024-06-19) |
| Primary citation | Aylott, H.E.,Atkinson, S.J.,Bamborough, P.,Bassil, A.,Chung, C.W.,Gordon, L.,Grandi, P.,Gray, J.R.J.,Harrison, L.A.,Hayhow, T.G.,Messenger, C.,Mitchell, D.,Phillipou, A.,Preston, A.,Prinjha, R.K.,Rianjongdee, F.,Rioja, I.,Seal, J.T.,Wall, I.D.,Watson, R.J.,Woolven, J.M.,Demont, E.H. Template-Hopping Approach Leads to Potent, Selective, and Highly Soluble Bromo and Extraterminal Domain (BET) Second Bromodomain (BD2) Inhibitors. J.Med.Chem., 64:3249-3281, 2021 Cited by PubMed Abstract: A number of reports have recently been published describing the discovery and optimization of bromo and extraterminal inhibitors which are selective for the second bromodomain (BD2); these include our own work toward GSK046 () and GSK620 (). This paper describes our approach to mitigating the genotoxicity risk of GSK046 by replacement of the acetamide functionality with a heterocyclic ring. This was followed by a template-hopping and hybridization approach, guided by structure-based drug design, to incorporate learnings from other BD2-selective series, optimize the vector for the amide region, and explore the ZA cleft, leading to the identification of potent, selective, and bioavailable compounds (GSK452), (GSK737), and (GSK217). PubMed: 33662213DOI: 10.1021/acs.jmedchem.0c02156 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
Download full validation report
