4a9y: Difference between revisions
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<StructureSection load='4a9y' size='340' side='right' caption='[[4a9y]], [[Resolution|resolution]] 2.20Å' scene=''> | <StructureSection load='4a9y' size='340' side='right' caption='[[4a9y]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a9y]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4a9y]] 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=4A9Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A9Y FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand= | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AQZ:N-(3-{[7-METHOXY-6-(2-PYRROLIDIN-1-YLETHOXY)QUINAZOLIN-4-YL]AMINO}-4-METHYLPHENYL)-2-MORPHOLIN-4-YLISONICOTINAMIDE'>AQZ</scene><br> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2baj|2baj]], [[1wfc|1wfc]], [[3zsi|3zsi]], [[1w7h|1w7h]], [[1wbo|1wbo]], [[1kv2|1kv2]], [[1yqj|1yqj]], [[1bmk|1bmk]], [[1bl7|1bl7]], [[1zyj|1zyj]], [[1a9u|1a9u]], [[1wbt|1wbt]], [[2i0h|2i0h]], [[3zs5|3zs5]], [[2yiw|2yiw]], [[2baq|2baq]], [[1zz2|1zz2]], [[1wbv|1wbv]], [[1di9|1di9]], [[1w83|1w83]], [[1bl6|1bl6]], [[3zsh|3zsh]], [[1m7q|1m7q]], [[1ian|1ian]], [[1oz1|1oz1]], [[1wbn|1wbn]], [[3zya|3zya]], [[2bak|2bak]], [[3zsg|3zsg]], [[2bal|2bal]], [[1wbs|1wbs]], [[1ouy|1ouy]], [[1ouk|1ouk]], [[2y8o|2y8o]], [[2yis|2yis]], [[1r39|1r39]], [[1wbw|1wbw]], [[1kv1|1kv1]], [[1w82|1w82]], [[2yix|2yix]], [[1ove|1ove]], [[1r3c|1r3c]], [[1zzl|1zzl]], [[1w84|1w84]]</td></tr> | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2baj|2baj]], [[1wfc|1wfc]], [[3zsi|3zsi]], [[1w7h|1w7h]], [[1wbo|1wbo]], [[1kv2|1kv2]], [[1yqj|1yqj]], [[1bmk|1bmk]], [[1bl7|1bl7]], [[1zyj|1zyj]], [[1a9u|1a9u]], [[1wbt|1wbt]], [[2i0h|2i0h]], [[3zs5|3zs5]], [[2yiw|2yiw]], [[2baq|2baq]], [[1zz2|1zz2]], [[1wbv|1wbv]], [[1di9|1di9]], [[1w83|1w83]], [[1bl6|1bl6]], [[3zsh|3zsh]], [[1m7q|1m7q]], [[1ian|1ian]], [[1oz1|1oz1]], [[1wbn|1wbn]], [[3zya|3zya]], [[2bak|2bak]], [[3zsg|3zsg]], [[2bal|2bal]], [[1wbs|1wbs]], [[1ouy|1ouy]], [[1ouk|1ouk]], [[2y8o|2y8o]], [[2yis|2yis]], [[1r39|1r39]], [[1wbw|1wbw]], [[1kv1|1kv1]], [[1w82|1w82]], [[2yix|2yix]], [[1ove|1ove]], [[1r3c|1r3c]], [[1zzl|1zzl]], [[1w84|1w84]]</td></tr> | ||
<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=4a9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9y RCSB], [http://www.ebi.ac.uk/pdbsum/4a9y PDBsum]</span></td></tr> | <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=4a9y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a9y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a9y RCSB], [http://www.ebi.ac.uk/pdbsum/4a9y PDBsum]</span></td></tr> | ||
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The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases.,Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W, Swallow S, Thompson C Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83. Epub 2012 May 2. PMID:22608965<ref>PMID:22608965</ref> | The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases.,Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W, Swallow S, Thompson C Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83. Epub 2012 May 2. PMID:22608965<ref>PMID:22608965</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Gerhardt, S.]] | [[Category: Gerhardt, S.]] | ||
[[Category: Hargreaves, D.]] | [[Category: Hargreaves, D.]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
Revision as of 08:45, 24 September 2014
P38ALPHA MAP KINASE BOUND TO CMPD 8P38ALPHA MAP KINASE BOUND TO CMPD 8
Structural highlights
Publication Abstract from PubMedA novel, potent and selective quinazolinone series of inhibitors of p38alpha MAP kinase has been identified. Modifications designed to address the issues of poor aqueous solubility and high plasma protein binding as well as embedded aniline functionalities resulted in the identification of a clinical candidate N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703). Optimisation was guided by understanding of the binding modes from X-ray crystallographic studies which showed a switch from DFG 'out' to DFG 'in' as the inhibitor size was reduced to improve overall properties. The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases.,Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W, Swallow S, Thompson C Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83. Epub 2012 May 2. PMID:22608965[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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