7DHS

Crystal Structure Analysis of the BRD4

Summary for 7DHS

• Entry DOI: 10.2210/pdb7dhs/pdb
• Descriptor: Bromodomain-containing protein 4, 6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R)-1-phenylethyl]benzo[cd]indol-2-one (3 entities in total)
• Functional Keywords: brd4, bromodomain, structural protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 34271.51

Authors

Wu, T.,Xiang, Q.,Wang, C.,Wu, C.,Zhang, C.,Zhang, M.,Liu, Z.,Zhang, Y.,Xiao, L.,Xu, Y. (deposition date: 2020-11-17, release date: 2021-09-15, Last modification date: 2023-11-29)

Primary citation

Wu, T.B.,Xiang, Q.P.,Wang, C.,Wu, C.,Zhang, C.,Zhang, M.F.,Liu, Z.X.,Zhang, Y.,Xiao, L.J.,Xu, Y.
Y06014 is a selective BET inhibitor for the treatment of prostate cancer.
Acta Pharmacol.Sin., 42:2120-2131, 2021

PubMed Abstract: Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.

PubMed: 33654218
DOI: 10.1038/s41401-021-00614-7

Experimental method

X-RAY DIFFRACTION (1.76 Å)