6v52
From Proteopedia
(Difference between revisions)
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<StructureSection load='6v52' size='340' side='right'caption='[[6v52]], [[Resolution|resolution]] 1.78Å' scene=''> | <StructureSection load='6v52' size='340' side='right'caption='[[6v52]], [[Resolution|resolution]] 1.78Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6v52]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V52 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V52 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6v52]] is a 2 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=6V52 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6V52 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QPV:3-chloro-N-{4-[1-(propylcarbamoyl)cyclobutyl]phenyl}benzamide'>QPV</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QPV:3-chloro-N-{4-[1-(propylcarbamoyl)cyclobutyl]phenyl}benzamide'>QPV</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IDO1, IDO, INDO ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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://proteopedia.org/fgij/fg.htm?mol=6v52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v52 OCA], [http://pdbe.org/6v52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v52 RCSB], [http://www.ebi.ac.uk/pdbsum/6v52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v52 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6v52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v52 OCA], [http://pdbe.org/6v52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v52 RCSB], [http://www.ebi.ac.uk/pdbsum/6v52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v52 ProSAT]</span></td></tr> | ||
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== Function == | == 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> | [[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 == | ||
| + | Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as a target of significant interest to the field of cancer immunotherapy, as the upregulation of IDO1 in certain cancers has been linked to host immune evasion and poor prognosis for patients. In particular, IDO1 inhibition is of interest as a combination therapy with immune checkpoint inhibition. Through an Automated Ligand Identification System (ALIS) screen, a diamide class of compounds was identified as a promising lead for the inhibition of IDO1. While hit 1 possessed attractive cell-based potency, it suffered from a significant right-shift in a whole blood assay, poor solubility, and poor pharmacokinetic properties. Through a physicochemical property-based approach, including a focus on lowering AlogP98 via the strategic introduction of polar substitution, compound 13 was identified bearing a pyridyl oxetane core. Compound 13 demonstrated improved whole blood potency and solubility, and an improved pharmacokinetic profile resulting in a low predicted human dose. | ||
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| + | Strategic Incorporation of Polarity in Heme-Displacing Inhibitors of Indoleamine-2,3-dioxygenase-1 (IDO1).,White C, McGowan MA, Zhou H, Sciammetta N, Fradera X, Lim J, Joshi EM, Andrews C, Nickbarg EB, Cowley P, Trewick S, Augustin M, von Koenig K, Lesburg CA, Otte K, Knemeyer I, Woo H, Yu W, Cheng M, Spacciapoli P, Geda P, Song X, Smotrov N, Curran P, Heo MR, Abeywickrema P, Miller JR, Bennett DJ, Han Y ACS Med Chem Lett. 2020 Mar 10;11(4):550-557. doi:, 10.1021/acsmedchemlett.0c00010. eCollection 2020 Apr 9. PMID:32292563<ref>PMID:32292563</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6v52" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Indoleamine 2,3-dioxygenase]] | [[Category: Indoleamine 2,3-dioxygenase]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
Current revision
IDO1 IN COMPLEX WITH COMPOUND 1
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