6o3i: Difference between revisions
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==Crystal Structure of Human IDO1 bound to navoximod (NLG-919)== | |||
<StructureSection load='6o3i' size='340' side='right'caption='[[6o3i]], [[Resolution|resolution]] 2.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6o3i]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6O3I OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6O3I FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=LKP:trans-4-{(1R)-2-[(5S)-6-fluoro-5H-imidazo[5,1-a]isoindol-5-yl]-1-hydroxyethyl}cyclohexan-1-ol'>LKP</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase Indoleamine 2,3-dioxygenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.13.11.52 1.13.11.52] </span></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=6o3i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o3i OCA], [http://pdbe.org/6o3i PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o3i RCSB], [http://www.ebi.ac.uk/pdbsum/6o3i PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o3i ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/I23O1_HUMAN I23O1_HUMAN]] Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.<ref>PMID:17671174</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A novel class of 5-substituted 5 H-imidazo[5,1- a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5 H-imidazo[5,1- a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties. | |||
Discovery of Clinical Candidate (1 R,4 r)-4-(( R)-2-(( S)-6-Fluoro-5 H-imidazo[5,1- a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1.,Kumar S, Waldo JP, Jaipuri FA, Marcinowicz A, Van Allen C, Adams J, Kesharwani T, Zhang X, Metz R, Oh AJ, Harris SF, Mautino MR J Med Chem. 2019 Jul 2. doi: 10.1021/acs.jmedchem.9b00662. PMID:31264862<ref>PMID:31264862</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6o3i" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Indoleamine 2,3-dioxygenase]] | |||
[[Category: Large Structures]] | |||
[[Category: Harris, S F]] | |||
[[Category: Oh, A]] | |||
[[Category: Dioxygenase]] | |||
[[Category: Ido]] | |||
[[Category: Oxidoreductase-inhibitor complex]] | |||
[[Category: Tdo]] | |||
[[Category: Tryptophan]] | |||
