1.14.13.9: kynurenine 3-monooxygenase
This is an abbreviated version!
For detailed information about kynurenine 3-monooxygenase, go to the full flat file.
Word Map on EC 1.14.13.9
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1.14.13.9
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mercury
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hg
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kynurenic
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3-hydroxykynurenine
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quinolinic
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2,3-dioxygenase
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kynureninase
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indoleamine
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cronbach
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huntington
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bartlett
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paint
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3-hydroxyanthranilic
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quin
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neuroactive
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ochre
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realgar
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psychometric
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calcite
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methylmercury
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xanthurenic
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eigenvalue
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vermilion
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hematite
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test-retest
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excitotoxins
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ommochrome
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artwork
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geochemical
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indoleamine-2,3-dioxygenase
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archaeological
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varimax
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roman
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mineralogical
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slovenia
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micro-raman
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molecular biology
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medicine
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analysis
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pharmacology
- 1.14.13.9
- mercury
- hg
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kynurenic
- 3-hydroxykynurenine
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quinolinic
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2,3-dioxygenase
- kynureninase
- indoleamine
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cronbach
- huntington
-
bartlett
-
paint
-
3-hydroxyanthranilic
-
quin
-
neuroactive
-
ochre
-
realgar
-
psychometric
-
calcite
- methylmercury
-
xanthurenic
-
eigenvalue
-
vermilion
-
hematite
-
test-retest
-
excitotoxins
-
ommochrome
-
artwork
-
geochemical
- indoleamine-2,3-dioxygenase
-
archaeological
-
varimax
-
roman
-
mineralogical
-
slovenia
-
micro-raman
- molecular biology
- medicine
- analysis
- pharmacology
Reaction
Synonyms
BcKMO, Bna4, cinnabar, EC 1.14.1.2, EC 1.99.1.5, FAD dependent kynurenine 3-monooxygenase, flavin adenine dinucleotide dependent kynurenine 3-monooxygenase, hKMO, Hs-KMO, K3H, KMO, KYN-OHase, kynurenine 3-hydroxylase, kynurenine 3-monooxygenase, kynurenine hydroxylase, kynurenine monooxygenase, kynurenine-3-monooxygenase, L-kynurenine 3-monooxygenase, L-kynurenine,NADPH2:oxygen oxidoreductase (3-hydroxylating), L-kynurenine-3-hydroxylase, More, NADPH-dependent flavin monooxygenase, oxygenase, kynurenine 3-mono-, pfKMO, Rat-KMO, scKMO
ECTree
1.14.13.9 kynurenine 3-monooxygenaseAdvanced search results
results (
results (Inhibitors
Inhibitors on EC 1.14.13.9 - kynurenine 3-monooxygenase
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INHIBITOR 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
IMAGE
(1S,2S)-2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
-
KMO inhibitor UPF 648, totally blocks KMO at 0.1 and 0.01 mM and is still highly active at 0.001 mM (81% inhibition). It reduces 3-hydroxykynurenine synthesis by 64% without affecting kynurenic acid formation. In neuron-depleted striata, UPF 648 decreases both 3-hydroxykynurenine and quinolinic acid production by 77% and 66%, respectively and also raises kynurenic acid synthesis by 27%. 0.1 mM UPF 648 blocks KMO in both lesioned and contralateral striatum, but does not interfere with KAT activity in either tissue
(R)-3-(5-chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
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(R,S)-2-amino-oxo-4-(3',4'-dichlorophenyl)butanoic acid
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FCE 28833, 50% inhibition at 0.2 microM, blocks not only the cerebral but also the peripheral enzyme
(S)-3-(5-Chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
-
(S)-9-(4-aminopiperazine-1-yl)-8-fluoro-3-methyl-6-oxo-2,3,5,6-tetrahydro-4H-1-oxa-3a-azaphenalene-5-carboxylic acid
-
does not affect KMO activity significantly, 1 mM inhibits by 17%
1-cyclopentyl-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)methanesulfonamide
-
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2,2,2-trifluoro-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethane-1-sulfonamide
-
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3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
-
3-(5,6-dichloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
-
3-(5-chloro-6-cyclopropoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
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3-(5-chloro-6-methoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
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3-(5-chloro-6-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
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3-[2-methylidene-5-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-(propan-2-yl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
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3-[5-chloro-2-oxo-6-(pyridin-2-ylmethoxy)-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-2-oxo-6-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridazin-3-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzothiazol-3-yl]propanoic acid
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3-[5-chloro-2-oxo-6-[(1R)-1-(pyrimidin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-2-oxo-6-[(propan-2-yl)oxy]-1,3-benzoxazol-3(2H)-yl]propanoic acid
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3-[5-chloro-2-oxo-6-[1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
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3-[5-chloro-2-oxo-6-[2-(pyrrolidin-1-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
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3-[5-chloro-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-(2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-(cyclobutylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-(cyclopropylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
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3-[5-chloro-6-(cyclopropyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(1,3-oxazol-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(4-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
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3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(6-methylpyridazin-3-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(6-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
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3-[6-(benzyloxy)-5-chloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
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3-[6-chloro-3-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-3,4-dihydro-2H-1,4-benzoxazin-4-yl]propanoic acid
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3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indazol-1-yl]propanoic acid
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3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indol-1-yl]-propanoic acid
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4-amino-N-[4-(2-fluoro-5-trifluoromethyl-phenyl)-thiazol-2-yl]-benzenesulfonamide
-
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4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide
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50% inhibition at 19nM
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
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4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
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4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
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4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
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4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
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4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
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7-chloro-3-methyl-1H-pyrrolo[3,2-c]quinoline-4-carboxylic acid
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relatively potent and selective inhibitor
benzoylalanine
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KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
ianthellamide A
an octopamine derivative isolated from the Australian marine sponge Ianthella quadrangulata, selectively inhibits KMO
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m-nitrobenzoylalanine
-
KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
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N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
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N-(6-[2-fluoro-6-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
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N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
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N-(6-[3-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
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N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-2-yl)methanesulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-3-yl)methanesulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-4-yl)methanesulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxolan-2-yl)methanesulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-2-methoxyethane-1-sulfonamide
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-3-methoxypropane-1-sulfonamide
-
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)butane-2-sulfonamide
-
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethanesulfonamide
-
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N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)propane-1-sulfonamide
-
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N-(6-[5-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
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N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
-
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N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
-
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N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
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(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
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(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
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(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
-
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(m-nitrobenzoyl)-alanine
-
mNBA, leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
(m-nitrobenzoyl)-alanine
-
mNBA, leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
(m-nitrobenzoyl)-alanine
-
various pyrrolo[3,2-c]quinoline derivates cause enzyme inhibition
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
UPF648, UPF648 prevents the binding of the native substrate KYN by binding closely to the FAD cofactor. In a transgenic Drosophila melanogaster model of Huntington's disease, UPF648 is shown to mitigate disease-relevant phenotypes. While UPF648 inhibits KMO, it also significantly increases the production of hydrogen peroxide by almost 20fold
-
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
UPF648, UPF648 prevents the binding of the native substrate KYN by binding closely to the FAD cofactor. Enzyme-binding structure determination (PDB ID 4J36) and further pharmacophore modeling
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2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
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2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
R380, a residue from the enzyme's C-terminal region, forms hydrogen bonds with the carboxylic acid moiety of the inhibitor, residues R85, Y99 and Y398 also form bonds to 2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro-61-8048
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
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3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview. Ro 61-8048-scKMO complex structure analysis
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
Ro-61-8048, shows a greater potency than the previously discussed native substrate analogue 3,4-dichlorobenzoyl alanine
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
Ro-61-8048, 50% inhibition at 37 nM
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
inhibition after oral or intraperitoneal administration
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
i.e. Ro 61-8048, high-affinity low molecular inhibitor
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
JM-6
-
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
JM-6
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
GSK-065
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
GSK-065
-
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
-
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
-
-
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
ligand-binding structure, overview
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
permeable and strong KMO inhibitor
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
CHDI-340246
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
CHDI-340246
-
Cl-
low concentrations of NaCl solution stabilize the enzyme and decrease the limiting rate of reduction by 30fold. This effect is specific to the Cl- anion. The rate of hydroxylation is also moderately reduced with the introduction of NaCl solution
Cl-
-
70% inhibition with 0.1 M NaCl or KCl, competitive with respect to NADPH and non-competitive with respect to L-kynurenine
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor. The compound exhibits high brain permeability and a long-lasting pharmacokinetics profile in monkeys. Enzyme inhibition leads to production of neuroprotective kynurenic acid in the brain
-
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor. The compound exhibits high brain permeability and a long-lasting pharmacokinetics profile in monkeys, and neuroprotective kynurenic acid is increased by a single administration of the inhibitor in R6/2 mouse brain
-
Ro 61-8048
noncompetitive. Theinhibitor is bound in the tunnel at the interface where the N- and C-terminal domains associate
UPF 648
UPF 648 binds close to the FAD cofactor and perturbs the local active site structure, preventing productive binding of the substrate kynurenine
ZINC19827377
the inhibitor does not cause hydrogen peroxide as a harmful side product
-
ZINC71915355
the inhibitor is both blood brain barrier permeable and does not cause hydrogen peroxide as a harmful side product
-
additional information
kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of kcat and kcat/Km comparable to or higher than kynurenine. Kynurenines substituted in the 3-position are competitive inhibitors, with KI values lower than the Km for kynurenine. Bromination also enhances inhibition. A pharmacophore model of kynurenine monooxygenase is developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor
-
additional information
-
kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of kcat and kcat/Km comparable to or higher than kynurenine. Kynurenines substituted in the 3-position are competitive inhibitors, with KI values lower than the Km for kynurenine. Bromination also enhances inhibition. A pharmacophore model of kynurenine monooxygenase is developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor
-
additional information
-
inhibition by various 2-amino-4-aryl-4-oxobut-2-enoic acids and esters at 10 micromolar; inhibition by various 4-aryl-2-hyroxy-4-oxobut-2-enoic acids and esters at 10 micromolar
-
additional information
the molecular mechanism of action of three classes of inhibitors with differentiated binding modes and kinetics is reported. Two inhibitor classes trap the catalytic flavin in a tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production
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additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
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additional information
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
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additional information
determinations of inhibition with the purified enzyme and a cell-based assay
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additional information
enzyme structure and ligand interaction analysis using the crystal structure of hKMO (PDB ID 5X68), library screening from Zinc15 database, detailed overview
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additional information
research focuses on the inhibition of key enzymes in the kynurenine pathway (KP) to shunt it towards a neuroprotective state, based on the assumption that kynurenic acid (KYNA) has neuroprotective abilities. While substrate analogues bind in the active site of KMO and inhibit activity, they also detrimentally result in the formation of cytotoxic hydrogen peroxide by uncoupling the reaction of NAD(P)H and O2
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additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
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additional information
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
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additional information
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pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
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additional information
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the specific enzyme activity is not affected by cloricromene in vitro and in vivo in liver and kidney
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additional information
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targeted inhibition of KMO is a viable strategy for achieving local elevation of kynurenate concentrations
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additional information
development and optimization of a series of inhibitors
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additional information
the molecular mechanism of action of three classes of inhibitors with differentiated binding modes and kinetics is reported. Two inhibitor classes trap the catalytic flavin in a tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production
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additional information
enzyme structure and ligand interaction analysis using the crystal structure of pfKMO (PDB ID 5NAK), library screening from Zinc15 database, detailed overview
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additional information
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inhibition by N-(4-phenylthiazol-2-yl)benzenesulfonamides with various modifications
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additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
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additional information
determinations of inhibition with the purified enzyme and a cell-based assay, docking studies of KMO representative inhibitors, inhibition mechanism, overview
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additional information
enzyme structure and ligand interaction analysis using the crystal structure of scKMO (PDB ID 4J34), library screening from Zinc15 database, detailed overview
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