| Structural highlights
Disease
[BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2]
Function
[BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
Publication Abstract from PubMed
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-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives were designed and synthesized as selective bromodomain containing protein 4 (BRD4) inhibitors. The compounds potently inhibit BRD4(1) with nanomolar IC50 values and exhibit high selectivity over most non-BET subfamily members. One of the representative compounds 36 (Y08060) effectively suppresses cell growth, colony formation, and expression of androgen receptor (AR), AR regulated genes, and MYC in prostate cancer cell lines. In in vivo studies, 36 demonstrates a good PK profile with high oral bioavailability (61.54%) and is a promising lead compound for further prostate cancer drug development.
Y08060: A Selective BET Inhibitor for Treatment of Prostate Cancer.,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 ACS Med Chem Lett. 2018 Feb 13;9(3):262-267. doi: 10.1021/acsmedchemlett.8b00003., eCollection 2018 Mar 8. PMID:29541371[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
- ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
- ↑ 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. 2018 Feb 13;9(3):262-267. doi: 10.1021/acsmedchemlett.8b00003., eCollection 2018 Mar 8. PMID:29541371 doi:http://dx.doi.org/10.1021/acsmedchemlett.8b00003
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