4x2i
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Discovery of benzotriazolo diazepines as orally-active inhibitors of BET bromodomains: Crystal structure of BRD4 with CPI-13== | |
| + | <StructureSection load='4x2i' size='340' side='right' caption='[[4x2i]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4x2i]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X2I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X2I FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3X0:(4R)-6-(4-CHLOROPHENYL)-1,4-DIMETHYL-5,6-DIHYDRO-4H-[1,2,4]TRIAZOLO[4,3-A][1,5]BENZODIAZEPINE'>3X0</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=4x2i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x2i OCA], [http://pdbe.org/4x2i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x2i RCSB], [http://www.ebi.ac.uk/pdbsum/4x2i PDBsum]</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 == | ||
| + | Inhibition of the bromodomains of the BET family, of which BRD4 is a member, has been shown to decrease myc and interleukin (IL) 6 in vivo, markers that are of therapeutic relevance to cancer and inflammatory disease, respectively. Herein we report substituted benzo[b]isoxazolo[4,5-d]azepines and benzotriazolo[4,3-d][1,4]diazepines as fragment-derived novel inhibitors of the bromodomain of BRD4. Compounds from these series were potent and selective in cells, and subsequent optimization of microsomal stability yielded representatives that demonstrated dose- and time-dependent reduction of plasma IL-6 in mice. | ||
| - | + | Discovery of Benzotriazolo[4,3-d][1,4]diazepines as Orally Active Inhibitors of BET Bromodomains.,Taylor AM, Vaswani RG, Gehling VS, Hewitt MC, Leblanc Y, Audia JE, Bellon S, Cummings RT, Cote A, Harmange JC, Jayaram H, Joshi S, Lora JM, Mertz JA, Neiss A, Pardo E, Nasveschuk CG, Poy F, Sandy P, Setser JW, Sims RJ 3rd, Tang Y, Albrecht BK ACS Med Chem Lett. 2015 Mar 25;7(2):145-50. doi: 10.1021/ml500411h. eCollection, 2016 Feb 11. PMID:26985289<ref>PMID:26985289</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4x2i" style="background-color:#fffaf0;"></div> |
| + | |||
| + | ==See Also== | ||
| + | *[[Bromodomain-containing protein|Bromodomain-containing protein]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bellon, S F]] | ||
[[Category: Jayaram, H]] | [[Category: Jayaram, H]] | ||
| - | [[Category: | + | [[Category: Poy, F]] |
| + | [[Category: Bet]] | ||
| + | [[Category: Cpi-13]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 16:54, 10 May 2016
Discovery of benzotriazolo diazepines as orally-active inhibitors of BET bromodomains: Crystal structure of BRD4 with CPI-13
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Categories: Bellon, S F | Jayaram, H | Poy, F | Bet | Cpi-13 | Signaling protein
