7OE5
C-TERMINAL BROMODOMAIN OF HUMAN BRD2 WITH N5-hydroxycyclohexyl-N3-methyl-1-phenylethyl-1H-pyrazole-3,5-dicarboxamide
This is a non-PDB format compatible entry.
Summary for 7OE5
| Entry DOI | 10.2210/pdb7oe5/pdb |
| Related | 7OE4 |
| Descriptor | Bromodomain-containing protein 2, 3N-methyl-5N-(4-oxidanylcyclohexyl)-1-[(1S)-1-phenylethyl]pyrazole-3,5-dicarboxamide, 1,2-ETHANEDIOL, ... (4 entities in total) |
| Functional Keywords | inhibitor, bromodomain, nuclear protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 13927.04 |
| Authors | Chung, C. (deposition date: 2021-05-01, release date: 2021-07-28, Last modification date: 2024-05-01) |
| Primary citation | Seal, J.T.,Atkinson, S.J.,Bamborough, P.,Bassil, A.,Chung, C.W.,Foley, J.,Gordon, L.,Grandi, P.,Gray, J.R.J.,Harrison, L.A.,Kruger, R.G.,Matteo, J.J.,McCabe, M.T.,Messenger, C.,Mitchell, D.,Phillipou, A.,Preston, A.,Prinjha, R.K.,Rianjongdee, F.,Rioja, I.,Taylor, S.,Wall, I.D.,Watson, R.J.,Woolven, J.M.,Wyce, A.,Zhang, X.P.,Demont, E.H. Fragment-based Scaffold Hopping: Identification of Potent, Selective, and Highly Soluble Bromo and Extra Terminal Domain (BET) Second Bromodomain (BD2) Inhibitors. J.Med.Chem., 64:10772-10805, 2021 Cited by PubMed Abstract: The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole (GSK809) and furan (GSK743) that were derived from the pyrrole fragment . We transpose the key learnings from a previous pyridone series (GSK620 as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research. PubMed: 34255512DOI: 10.1021/acs.jmedchem.1c00365 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.602 Å) |
Structure validation
Download full validation report
