5z1t
From Proteopedia
(Difference between revisions)
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==Crystal Structure Analysis of the BRD4(1)== | ==Crystal Structure Analysis of the BRD4(1)== | ||
| - | <StructureSection load='5z1t' size='340' side='right' caption='[[5z1t]], [[Resolution|resolution]] 1.42Å' scene=''> | + | <StructureSection load='5z1t' size='340' side='right'caption='[[5z1t]], [[Resolution|resolution]] 1.42Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5z1t]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1T FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5z1t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Z1T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z1T FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFN:5-bromo-N-(6-hydroxy-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EFN:5-bromo-N-(6-hydroxy-2,2-dimethyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-yl)-2-methoxybenzene-1-sulfonamide'>EFN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5z1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1t OCA], [http://pdbe.org/5z1t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1t RCSB], [http://www.ebi.ac.uk/pdbsum/5z1t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1t ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5z1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z1t OCA], [http://pdbe.org/5z1t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z1t RCSB], [http://www.ebi.ac.uk/pdbsum/5z1t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z1t ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | [[http://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 == | ||
| + | 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<ref>PMID:29541371</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5z1t" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Song, M]] | [[Category: Song, M]] | ||
[[Category: Wang, C]] | [[Category: Wang, C]] | ||
Revision as of 08:31, 24 July 2019
Crystal Structure Analysis of the BRD4(1)
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Categories: Human | Large Structures | Song, M | Wang, C | Xiang, Q | Xu, Y | Zhang, Y | Bromodomain | Transcription
