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6o3i

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Crystal Structure of Human IDO1 bound to navoximod (NLG-919)

Structural highlights

6o3i is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	IDO1, IDO, INDO (HUMAN)
Activity:	Indoleamine 2,3-dioxygenase, with EC number 1.13.11.52
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[I23O1_HUMAN] Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Metz R, Duhadaway JB, Kamasani U, Laury-Kleintop L, Muller AJ, Prendergast GC. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res. 2007 Aug 1;67(15):7082-7. PMID:17671174 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-1872
↑ 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. 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. J Med Chem. 2019 Jul 2. doi: 10.1021/acs.jmedchem.9b00662. PMID:31264862 doi:http://dx.doi.org/10.1021/acs.jmedchem.9b00662

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6o3i"

@@ Line 3: / Line 3: @@
 <StructureSection load='6o3i' size='340' side='right'caption='[[6o3i]], [[Resolution|resolution]] 2.69&Aring;' 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>
+<table><tr><td colspan='2'>[[6o3i]] 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=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='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='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>
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Indoleamine 2,3-dioxygenase]]
 [[Category: Large Structures]]

6o3i

From Proteopedia

Current revision

Crystal Structure of Human IDO1 bound to navoximod (NLG-919)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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