| 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
Pan-BET inhibitors interact equipotently with all eight bromodomains of the BET family of proteins. They have shown profound efficacy in-vitro and in-vivo in oncology and immuno-modulatory models and a number are currently in clinical trials where significant safety signals have been reported. It is therefore important to understand the functional contribution of each bromodomain to assess the opportunity to tease apart efficacy and toxicity. This article discloses the in-vitro and cellular activity profile of GSK789, a potent, cell permeable and highly selective inhibitor of the first bromodomains of the BET family.
GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins.,Watson RJ, Bamborough P, Barnett HA, Chung CW, Davis R, Gordon LJ, Grandi P, Petretich M, Phillipou A, Prinjha RK, Rioja I, Soden P, Werner T, Demont EH J Med Chem. 2020 Jul 21. doi: 10.1021/acs.jmedchem.0c00614. PMID:32691589[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Watson RJ, Bamborough P, Barnett HA, Chung CW, Davis R, Gordon LJ, Grandi P, Petretich M, Phillipou A, Prinjha RK, Rioja I, Soden P, Werner T, Demont EH. GSK789: A Selective Inhibitor of the First Bromodomains (BD1) of the Bromo and Extra Terminal Domain (BET) Proteins. J Med Chem. 2020 Jul 21. doi: 10.1021/acs.jmedchem.0c00614. PMID:32691589 doi:http://dx.doi.org/10.1021/acs.jmedchem.0c00614
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