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kynurenine 3-monooxygenase

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2886

Nomenclature: kynurenine 3-monooxygenase

Family: 1.14.13.9 Kynurenine 3-monooxygenase

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 486 1q43 KMO kynurenine 3-monooxygenase 1
Mouse 2 479 1 H3 Kmo kynurenine 3-monooxygenase
Rat 2 478 13q25 Kmo kynurenine 3-monooxygenase
Previous and Unofficial Names Click here for help
kynurenine 3-hydroxylase | kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
Database Links Click here for help
Alphafold O15229 (Hs), Q91WN4 (Mm), O88867 (Rn)
BRENDA 1.14.13.9
CATH/Gene3D 3.50.50.60
ChEMBL Target CHEMBL2145 (Hs), CHEMBL3407318 (Mm), CHEMBL3457 (Rn)
Ensembl Gene ENSG00000117009 (Hs), ENSMUSG00000039783 (Mm), ENSRNOG00000003709 (Rn), ENSG00000117009, ENSRNOG00000003709
Entrez Gene 8564 (Hs), 98256 (Mm), 59113 (Rn)
Human Protein Atlas ENSG00000117009 (Hs)
KEGG Enzyme 1.14.13.9
KEGG Gene hsa:8564 (Hs), mmu:98256 (Mm), rno:59113 (Rn)
OMIM 603538 (Hs)
Pharos O15229 (Hs)
RefSeq Nucleotide NM_003679 (Hs), NM_133809 (Mm), NM_021593 (Rn)
RefSeq Protein NP_003670 (Hs), NP_598570 (Mm), NP_067604 (Rn)
UniProtKB O15229 (Hs), Q91WN4 (Mm), O88867 (Rn)
Wikipedia KMO (Hs)
Enzyme Reaction Click here for help
EC Number: 1.14.13.9
Description Reaction Reference
L-kynurenine + NADPH + O2 <=> 3-hydroxy-L-kynurenine + NADP(+) + H2O

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK065 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 10.3 pKi 2
⤷ pKi 10.3 (Ki 5x10-11 M) [2]
GSK065 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 2
⤷ pIC50 8.6 (IC50 2.5x10-9 M) [2]
GSK180 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 8.2 pIC50 3
⤷ pIC50 8.2 [3]
Description: Biochemical assay using human KMO expressed as a GST-fusion protein in a baculovirus expression system.
Immunopharmacology Comments
GSK180-induced inhibition of KMO prevents multiple organ failure in rodent models of acute pancreatitis which is caused by excessive alcohol consumption [3], and which is an inflammatory condition in humans for which there is no current therapy. A Phase 1 trial of GSK's clinical stage KMO inhibitor GSK065/GSK3335065 in healthy subjects was terminated (see NCT03245619).
Immuno Process Associations
Immuno Process:  Cytokine production & signalling

References

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1. Alberati-Giani D, Cesura AM, Broger C, Warren WD, Röver S, Malherbe P. (1997) Cloning and functional expression of human kynurenine 3-monooxygenase. FEBS Lett, 410 (2-3): 407-12. [PMID:9237672]

2. Hutchinson JP, Rowland P, Taylor MRD, Christodoulou EM, Haslam C, Hobbs CI, Holmes DS, Homes P, Liddle J, Mole DJ et al.. (2017) Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. Nat Commun, 8: 15827. [PMID:28604669]

3. Mole DJ, Webster SP, Uings I, Zheng X, Binnie M, Wilson K, Hutchinson JP, Mirguet O, Walker A, Beaufils B et al.. (2016) Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis. Nat Med, 22 (2): 202-9. [PMID:26752518]

How to cite this page

1.14.13.9 Kynurenine 3-monooxygenase: kynurenine 3-monooxygenase. Last modified on 08/04/2019. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2886.