View source for 7dhs


==Crystal Structure Analysis of the BRD4==
<StructureSection load='7dhs' size='340' side='right'caption='[[7dhs]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dhs]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H8C:6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R)-1-phenylethyl]benzo[cd]indol-2-one'>H8C</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7dhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dhs OCA], [https://pdbe.org/7dhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dhs RCSB], [https://www.ebi.ac.uk/pdbsum/7dhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dhs ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/BRD4_HUMAN 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.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> 
== Function ==
[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

Y06014 is a selective BET inhibitor for the treatment of prostate cancer.,Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218<ref>PMID:33654218</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dhs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Liu Z]]
[[Category: Wang C]]
[[Category: Wu C]]
[[Category: Wu T]]
[[Category: Xiang Q]]
[[Category: Xiao L]]
[[Category: Xu Y]]
[[Category: Zhang C]]
[[Category: Zhang M]]
[[Category: Zhang Y]]