5yqx

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==Crystal Structure Analysis of the BRD4==
==Crystal Structure Analysis of the BRD4==
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<StructureSection load='5yqx' size='340' side='right' caption='[[5yqx]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
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<StructureSection load='5yqx' size='340' side='right'caption='[[5yqx]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5yqx]] 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=5YQX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YQX FirstGlance]. <br>
<table><tr><td colspan='2'>[[5yqx]] 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=5YQX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YQX FirstGlance]. <br>
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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).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The bromodomain and extra-terminal proteins (BET) have emerged as promising therapeutic targets for the treatment of castration-resistant prostate cancer (CRPC). We report the design, synthesis and evaluation of a new series of benzoxazinone-containing 3,5-dimethylisoxazole derivatives as selective BET inhibitors. One of the new compounds, (R)-12 (Y02234), binds to BRD4(1) with a Kd value of 110nM and blocks bromodomain and acetyl lysine interactions with an IC50 value of 100nM. It also exhibits selectivity for BET over non-BET bromodomain proteins and demonstrates reasonable anti-proliferation and colony formation inhibition effect in prostate cancer cell lines such as 22Rv1 and C4-2B. The BRD4 inhibitor (R)-12 also significantly suppresses the expression of ERG, Myc and AR target gene PSA at the mRNA level in prostate cancer cells. Treatment with (R)-12 significantly suppresses the tumor growth of prostate cancer (TGI=70%) in a 22Rv1-derived xenograft model. These data suggest that compound (R)-12 is a promising lead compound for the development of a new class of therapeutics for the treatment of CRPC.
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Benzoxazinone-containing 3,5-dimethylisoxazole derivatives as BET bromodomain inhibitors for treatment of castration-resistant prostate cancer.,Xue X, Zhang Y, Wang C, Zhang M, Xiang Q, Wang J, Wang A, Li C, Zhang C, Zou L, Wang R, Wu S, Lu Y, Chen H, Ding K, Li G, Xu Y Eur J Med Chem. 2018 May 25;152:542-559. doi: 10.1016/j.ejmech.2018.04.034. Epub , 2018 Apr 21. PMID:29758518<ref>PMID:29758518</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 5yqx" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Song, M]]
[[Category: Song, M]]
[[Category: Wang, C]]
[[Category: Wang, C]]

Revision as of 06:06, 12 June 2019

Crystal Structure Analysis of the BRD4

PDB ID 5yqx

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