kynurenine 3-monooxygenase | 1.14.13.9 Kynurenine 3-monooxygenase | IUPHAR Guide to IMMUNOPHARMACOLOGY

Top ▲

kynurenine 3-monooxygenase

  Target has curated data in GtoImmuPdb

Target id: 2886

Nomenclature: kynurenine 3-monooxygenase

Family: 1.14.13.9 Kynurenine 3-monooxygenase

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 2 486 1q42-q44 KMO kynurenine 3-monooxygenase 1
Mouse 2 479 1 H4 Kmo kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
Rat 2 478 13q25 Kmo kynurenine 3-monooxygenase
Previous and Unofficial Names
kynurenine 3-hydroxylase | kynurenine 3-monooxygenase (kynurenine 3-hydroxylase)
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 1.14.13.9
Description Reaction Reference
L-kynurenine + NADPH + O2 <=> 3-hydroxy-L-kynurenine + NADP(+) + H2O

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK065 Hs Inhibition 10.3 pKi 2
pKi 10.3 (Ki 5x10-11 M) [2]
GSK065 Hs Inhibition 8.6 pIC50 2
pIC50 8.6 (IC50 2.5x10-9 M) [2]
GSK180 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
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0071347 cellular response to interleukin-1 IEA

References

Show »

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 22/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2886.