6moa

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==C-terminal bromodomain of human BRD2 in complex with 4-(2-cyclopropyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole inhibitor==
==C-terminal bromodomain of human BRD2 in complex with 4-(2-cyclopropyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole inhibitor==
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<StructureSection load='6moa' size='340' side='right' caption='[[6moa]], [[Resolution|resolution]] 1.27&Aring;' scene=''>
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<StructureSection load='6moa' size='340' side='right'caption='[[6moa]], [[Resolution|resolution]] 1.27&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6moa]] 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=6MOA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MOA FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6moa]] is a 1 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=6MOA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MOA FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JW4:4-(2-cyclopropyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole'>JW4</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.271&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JW4:4-(2-cyclopropyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole'>JW4</scene></td></tr>
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<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=6moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6moa OCA], [http://pdbe.org/6moa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6moa RCSB], [http://www.ebi.ac.uk/pdbsum/6moa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6moa ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6moa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6moa OCA], [https://pdbe.org/6moa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6moa RCSB], [https://www.ebi.ac.uk/pdbsum/6moa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6moa ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
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[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref>
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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 (BET) family of proteins, consisting of the bromodomains containing protein 2 (BRD2), BRD3, BRD4, and the testis-specific BRDT, are key epigenetic regulators of gene transcription and has emerged as an attractive target for anticancer therapy. Herein, we describe the discovery of a novel potent BET bromodomain inhibitor, using a systematic structure-based approach focused on improving potency, metabolic stability, and permeability. The optimized dimethylisoxazole aryl-benzimidazole inhibitor exhibited high potency towards BRD4 and related BET proteins in biochemical and cell-based assays and inhibited tumor growth in two proof-of-concept preclinical animal models.
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Structure-guided discovery of a novel, potent, and orally bioavailable 3,5-dimethylisoxazole aryl-benzimidazole BET bromodomain inhibitor.,Sperandio D, Aktoudianakis V, Babaoglu K, Chen X, Elbel K, Chin G, Corkey B, Du J, Jiang B, Kobayashi T, Mackman R, Martinez R, Yang H, Zablocki J, Kusam S, Jordan K, Webb H, Bates JG, Lad L, Mish M, Niedziela-Majka A, Metobo S, Sapre A, Hung M, Jin D, Fung W, Kan E, Eisenberg G, Larson N, Newby ZER, Lansdon E, Tay C, Neve RM, Shevick SL, Breckenridge DG Bioorg Med Chem. 2019 Feb 1;27(3):457-469. doi: 10.1016/j.bmc.2018.11.020. Epub, 2018 Nov 15. PMID:30606676<ref>PMID:30606676</ref>
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==See Also==
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
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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 6moa" style="background-color:#fffaf0;"></div>
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== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
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[[Category: Lansdon, E B]]
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[[Category: Large Structures]]
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[[Category: Newby, Z E.R]]
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[[Category: Lansdon EB]]
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[[Category: Bromodomain]]
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[[Category: Newby ZER]]
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[[Category: Epigenetic reader]]
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[[Category: Inhibitor]]
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[[Category: Transcription-transcription inhibitor complex]]
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Current revision

C-terminal bromodomain of human BRD2 in complex with 4-(2-cyclopropyl-7-(6-methylquinolin-5-yl)-1H-benzo[d]imidazol-5-yl)-3,5-dimethylisoxazole inhibitor

PDB ID 6moa

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OCA

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