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==Crystal structure of COX-2 with selective compound 23d-(R)== | |||
<StructureSection load='3ntg' size='340' side='right'caption='[[3ntg]], [[Resolution|resolution]] 2.19Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ntg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NTG FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.19Å</td></tr> | ||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=D72:(2R)-6,8-DICHLORO-7-(2-METHYLPROPOXY)-2-(TRIFLUOROMETHYL)-2H-CHROMENE-3-CARBOXYLIC+ACID'>D72</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ntg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ntg OCA], [https://pdbe.org/3ntg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ntg RCSB], [https://www.ebi.ac.uk/pdbsum/3ntg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ntg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34h. | |||
The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life.,Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JR, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, Kiefer JR, Carter J Bioorg Med Chem Lett. 2010 Jul 24. PMID:20709553<ref>PMID:20709553</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ntg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Carter | [[Category: Carter JC]] | ||
[[Category: Graneto | [[Category: Graneto MJ]] | ||
[[Category: Kiefer | [[Category: Kiefer JR]] | ||
[[Category: Limburg | [[Category: Limburg D]] | ||
[[Category: Talley | [[Category: Talley JJ]] | ||
[[Category: Wang | [[Category: Wang JL]] | ||
Latest revision as of 03:33, 28 December 2023
Crystal structure of COX-2 with selective compound 23d-(R)Crystal structure of COX-2 with selective compound 23d-(R)
Structural highlights
FunctionPGH2_MOUSE Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.[1] [2] [3] [4] Publication Abstract from PubMedIn this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. During the course of our structure-based drug design efforts, we discovered two distinct binding modes within the COX-2 active site for differently substituted members of this class. The challenge of a undesirably long human half-life for the first clinical candidate 1t(1/2)=360h was addressed by multiple strategies, leading to the discovery of 29b-(S) (SC-75416) with t(1/2)=34h. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life.,Wang JL, Limburg D, Graneto MJ, Springer J, Hamper JR, Liao S, Pawlitz JL, Kurumbail RG, Maziasz T, Talley JJ, Kiefer JR, Carter J Bioorg Med Chem Lett. 2010 Jul 24. PMID:20709553[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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