5Z1S

Crystal Structure Analysis of the BRD4(1)

Summary for 5Z1S

• Entry DOI: 10.2210/pdb5z1s/pdb
• Descriptor: Bromodomain-containing protein 4, 5-bromo-2-methoxy-N-(6-methoxy-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)benzene-1-sulfonamide, NITRATE ION, ... (6 entities in total)
• Functional Keywords: brd4(1), bromodomain, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 17640.96

Authors

Xu, Y.,Zhang, Y.,Xiang, Q.,Song, M.,Wang, C. (deposition date: 2017-12-28, release date: 2019-01-02, Last modification date: 2024-03-27)

Primary citation

Xiang, Q.,Zhang, Y.,Li, J.,Xue, X.,Wang, C.,Song, M.,Zhang, C.,Wang, R.,Li, C.,Wu, C.,Zhou, Y.,Yang, X.,Li, G.,Ding, K.,Xu, Y.
Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.
Acs Med.Chem.Lett., 9:262-267, 2018

PubMed Abstract: Prostate cancer is a commonly diagnosed cancer and a leading cause of cancer-related deaths. The bromodomain and extra terminal domain (BET) family proteins have emerged as potential therapeutic targets for the treatment of castration-resistant prostate cancer. A series of 2,2-dimethyl-2-benzo[][1,4]oxazin-3(4)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In studies, demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.

PubMed: 29541371
DOI: 10.1021/acsmedchemlett.8b00003

Experimental method

X-RAY DIFFRACTION (1.42 Å)