6KEJ
Crystal structure of BRD4 bromodomain 1 (BD1) in complex with 6-[2-(diethylamino)ethoxy]-16-methoxy-11-methyl-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(17),3,5,7,9,13,15-heptaen-12-one
Summary for 6KEJ
| Entry DOI | 10.2210/pdb6kej/pdb |
| Descriptor | Bromodomain-containing protein 4, 6-[2-(diethylamino)ethoxy]-16-methoxy-11-methyl-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(17),3,5,7,9,13,15-heptaen-12-one, FORMIC ACID, ... (4 entities in total) |
| Functional Keywords | brd4, bromodomain 1, transcription |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 15511.75 |
| Authors | Lee, B.I.,Park, T.H. (deposition date: 2019-07-04, release date: 2020-07-08, Last modification date: 2023-11-22) |
| Primary citation | Yoo, M.,Park, T.H.,Yoo, M.,Kim, Y.,Lee, J.Y.,Lee, K.M.,Ryu, S.E.,Lee, B.I.,Jung, K.Y.,Park, C.H. Synthesis and Structure-Activity Relationships of Aristoyagonine Derivatives as Brd4 Bromodomain Inhibitors with X-ray Co-Crystal Research. Molecules, 26:-, 2021 Cited by PubMed Abstract: Epigenetic regulation is known to play a key role in progression of anti-cancer therapeutics. Lysine acetylation is an important mechanism in controlling gene expression. There has been increasing interest in bromodomain owing to its ability to modulate transcription of various genes as an epigenetic 'reader.' Herein, we report the design, synthesis, and X-ray studies of novel aristoyagonine (benzo[6,7]oxepino[4,3,2-]isoindol-2(1)-one) derivatives and investigate their inhibitory effect against Brd4 bromodomain. Five compounds , , , , and have been discovered with high binding affinity over the Brd4 protein. Co-crystal structures of these five inhibitors with human Brd4 bromodomain demonstrated that it has a key binding mode occupying the hydrophobic pocket, which is known to be the acetylated lysine binding site. These novel Brd4 bromodomain inhibitors demonstrated impressive inhibitory activity and mode of action for the treatment of cancer diseases. PubMed: 33802888DOI: 10.3390/molecules26061686 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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