5wuu: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5wuu is ~~ON HOLD~~ ~~until Paper~~ Publication

==Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring==

== Structural highlights ==

<table><tr><td colspan='2'>[[5wuu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WUU FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7UU:~{N}-METHYL-~{N}-[3-[(2-OXIDANYLIDENECHROMEN-4-YL)AMINO]PROPYL]THIOPHENE-2-CARBOXAMIDE'>7UU</scene></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=5wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuu OCA], [http://pdbe.org/5wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuu RCSB], [http://www.ebi.ac.uk/pdbsum/5wuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuu ProSAT]</span></td></tr>

</table>

== Disease ==

[[http://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 ==

[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

== Publication Abstract from PubMed ==

As an epigenetic reader, BRD4 regulates the transcription of important downstream genes that are essential for the survival of tumor cells. Small molecular inhibitors targeting the first bromodomain of BRD4 (BRD4-BD1) have showed promising potentials in the therapies of BRD4-related cancers. Through AlphaScreen-based high-throughput screening assay, a novel small molecular inhibitor was identified, and named DCBD-005, which inhibited the binding between BRD4-BD1 and acetylated lysines with an IC50 value of 0.81+/-0.03muM. The compound DCBD-005 effectively inhibited the viability, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Moreover, the crystal structure of compound DCBD-005 with the BRD4-BD1 was determined at 1.72A resolution, which revealed the binding mechanism of the leading compound, and also provided solid basis for further structure-based optimization. These results indicated that this novel BRD4-BD1 inhibitor DCBD-005 is promising to be developed into a drug candidate in the treatment of BRD4-related diseases.

~~Authors: Zhang~~, H., Sun, Z.Y.

Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays.,Sun Z, Zhang H, Chen Z, Xie Y, Jiang H, Chen L, Ding H, Zhang Y, Jiang H, Zheng M, Luo C Bioorg Med Chem Lett. 2017 May 1;27(9):2003-2009. doi:, 10.1016/j.bmcl.2017.03.012. Epub 2017 Mar 9. PMID:28347667<ref>PMID:28347667</ref>

~~Description: Complex structure~~ of the ~~first bromodomain~~ of ~~BRD4 with an inhibitor that containing a 2H~~-~~chromen~~-~~2-one ring~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Sun, Z Y]]

[[Category: Zhang, H]]

[[Category: ~~Sun, Z.Y~~]]

[[Category: Brd4]]

[[Category: Complex]]

[[Category: Inhibitor]]

[[Category: Transcription]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5wuu is ON HOLD  until Paper Publication
+==Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring==
+<StructureSection load='5wuu' size='340' side='right' caption='[[5wuu]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5wuu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WUU FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7UU:~{N}-METHYL-~{N}-[3-[(2-OXIDANYLIDENECHROMEN-4-YL)AMINO]PROPYL]THIOPHENE-2-CARBOXAMIDE'>7UU</scene></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=5wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuu OCA], [http://pdbe.org/5wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuu RCSB], [http://www.ebi.ac.uk/pdbsum/5wuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuu ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://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 ==
+[[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 ==
+As an epigenetic reader, BRD4 regulates the transcription of important downstream genes that are essential for the survival of tumor cells. Small molecular inhibitors targeting the first bromodomain of BRD4 (BRD4-BD1) have showed promising potentials in the therapies of BRD4-related cancers. Through AlphaScreen-based high-throughput screening assay, a novel small molecular inhibitor was identified, and named DCBD-005, which inhibited the binding between BRD4-BD1 and acetylated lysines with an IC50 value of 0.81+/-0.03muM. The compound DCBD-005 effectively inhibited the viability, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Moreover, the crystal structure of compound DCBD-005 with the BRD4-BD1 was determined at 1.72A resolution, which revealed the binding mechanism of the leading compound, and also provided solid basis for further structure-based optimization. These results indicated that this novel BRD4-BD1 inhibitor DCBD-005 is promising to be developed into a drug candidate in the treatment of BRD4-related diseases.
-Authors: Zhang, H., Sun, Z.Y.
+Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays.,Sun Z, Zhang H, Chen Z, Xie Y, Jiang H, Chen L, Ding H, Zhang Y, Jiang H, Zheng M, Luo C Bioorg Med Chem Lett. 2017 May 1;27(9):2003-2009. doi:, 10.1016/j.bmcl.2017.03.012. Epub 2017 Mar 9. PMID:28347667<ref>PMID:28347667</ref>
-Description: Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5wuu" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Sun, Z Y]]
 [[Category: Zhang, H]]
-[[Category: Sun, Z.Y]]
+[[Category: Brd4]]
+[[Category: Complex]]
+[[Category: Inhibitor]]
+[[Category: Transcription]]