2yex

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[[Image:2yex.jpg|left|200px]]
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==Synthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors==
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<StructureSection load='2yex' size='340' side='right' caption='[[2yex]], [[Resolution|resolution]] 1.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2yex]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YEX OCA]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YEX:5-METHYL-8-(1H-PYRROL-2-YL)[1,2,4]TRIAZOLO[4,3-A]QUINOLIN-1(2H)-ONE'>YEX</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ia8|1ia8]], [[1nvq|1nvq]], [[1nvr|1nvr]], [[1nvs|1nvs]], [[1zlt|1zlt]], [[1zys|1zys]], [[2ayp|2ayp]], [[2br1|2br1]], [[2brb|2brb]], [[2brg|2brg]], [[2brh|2brh]], [[2brm|2brm]], [[2brn|2brn]], [[2bro|2bro]], [[2c3j|2c3j]], [[2c3k|2c3k]], [[2c3l|2c3l]], [[2cgu|2cgu]], [[2cgv|2cgv]], [[2cgw|2cgw]], [[2cgx|2cgx]], [[2wmq|2wmq]], [[2wmr|2wmr]], [[2wms|2wms]], [[2wmt|2wmt]], [[2wmu|2wmu]], [[2wmv|2wmv]], [[2wmw|2wmw]], [[2wmx|2wmx]], [[2x8d|2x8d]], [[2x8e|2x8e]], [[2x8i|2x8i]], [[2xey|2xey]], [[2xez|2xez]], [[2xf0|2xf0]], [[2ydi|2ydi]], [[2ydj|2ydj]], [[2ydk|2ydk]], [[2yer|2yer]], [[2ym3|2ym3]], [[2ym4|2ym4]], [[2ym5|2ym5]], [[2ym6|2ym6]], [[2ym7|2ym7]], [[2ym8|2ym8]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2yex FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2yex OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2yex RCSB], [http://www.ebi.ac.uk/pdbsum/2yex PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Checkpoint kinase 1 (Chk1, CHEK1) is a Ser/Thr protein kinase that plays a key role in mediating the cellular response to DNA-damage. Synthesis and evaluation of a previously described class of Chk1 inhibitors, triazoloquinolones/triazolones (TZs) is further described herein. Our investigation of structure-activity relationships led to the identification of potent inhibitors 14c, 14h and 16e. Key challenges included modulation of physicochemical properties and pharmacokinetic (PK) parameters to enable compound testing in a Chk1 specific hollow fiber pharmacodynamic model. In this model, 16e was shown to abrogate topotecan-induced cell cycle arrest in a dose dependent manner. The demonstrated activity of TZs in this model in combination with a chemotherapeutic agent as well as radiotherapy validates this series of Chk1 inhibitors. X-ray crystal structures (PDB code: 2YEX and 2YER) for an initial lead and an optimized analog are also presented.
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Synthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors.,Oza V, Ashwell S, Brassil P, Breed J, Ezhuthachan J, Deng C, Grondine M, Horn C, Liu D, Lyne P, Newcombe N, Pass M, Read J, Su M, Toader D, Yu D, Yu Y, Zabludoff S Bioorg Med Chem Lett. 2012 Mar 15;22(6):2330-7. Epub 2012 Feb 1. PMID:22342147<ref>PMID:22342147</ref>
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The line below this paragraph, containing "STRUCTURE_2yex", creates the "Structure Box" on the page.
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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or leave the SCENE parameter empty for the default display.
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{{STRUCTURE_2yex| PDB=2yex | SCENE= }}
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===Synthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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The line below this paragraph, {{ABSTRACT_PUBMED_22342147}}, adds the Publication Abstract to the page
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__TOC__
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(as it appears on PubMed at http://www.pubmed.gov), where 22342147 is the PubMed ID number.
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</StructureSection>
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{{ABSTRACT_PUBMED_22342147}}
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==About this Structure==
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[[2yex]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2YEX OCA].
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==Reference==
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<ref group="xtra">PMID:022342147</ref><ref group="xtra">PMID:020673630</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 07:53, 14 May 2014

Synthesis and evaluation of triazolones as checkpoint kinase 1 inhibitors

2yex, resolution 1.30Å

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