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Literature summary for 1.14.13.9 extracted from

  • Kimura, H.; Suda, H.; Kassai, M.; Endo, M.; Deai, Y.; Yahata, M.; Miyajima, M.; Isobe, Y.
    N-(6-phenylpyridazin-3-yl)benzenesulfonamides as highly potent, brain-permeable, and orally active kynurenine monooxygenase inhibitors (2021), Bioorg. Med. Chem. Lett., 33, 127753 .
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
-
Mus musculus
2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid PNU-168754 Mus musculus
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide Ro-61-8048 Mus musculus
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide JM-6 Mus musculus
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid GSK-065 Mus musculus
3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
Mus musculus
4-methyl-N-[6-(quinolin-8-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
Mus musculus
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid CHDI-340246 Mus musculus
CHDI-340246
-
Mus musculus
additional information synthesis and evaluation of enzyme inhibitors Mus musculus
N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
Mus musculus
N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
Mus musculus
N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
Mus musculus
N-[6-(2-ethylphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
Mus musculus
N-[6-(2-methoxyphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-methylbenzene-1-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-2-sulfonamide
-
Mus musculus
N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-3-sulfonamide
-
Mus musculus
N-[6-(isoquinolin-8-yl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
Mus musculus
-
-
mitochondrial membrane
-
Mus musculus 31966
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-kynurenine + NADPH + H+ + O2 Mus musculus
-
3-hydroxy-L-kynurenine + NADP+ + H2O
-
?
L-kynurenine + NADPH + H+ + O2 Mus musculus R6/2
-
3-hydroxy-L-kynurenine + NADP+ + H2O
-
?

Organism

Organism UniProt Comment Textmining
Mus musculus Q91WN4
-
-
Mus musculus R6/2 Q91WN4
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
-
liver
-
Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-kynurenine + NADPH + H+ + O2
-
Mus musculus 3-hydroxy-L-kynurenine + NADP+ + H2O
-
?
L-kynurenine + NADPH + H+ + O2
-
Mus musculus R6/2 3-hydroxy-L-kynurenine + NADP+ + H2O
-
?

Synonyms

Synonyms Comment Organism
KMO
-
Mus musculus
kynurenine monooxygenase
-
Mus musculus

Cofactor

Cofactor Comment Organism Structure
FAD
-
Mus musculus
NADPH
-
Mus musculus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000005
-
pH and temperature not specified in the publication Mus musculus 6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
0.0000014
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
0.0000023
-
pH and temperature not specified in the publication Mus musculus 3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
0.0000026
-
brain enzyme, pH and temperature not specified in the publication Mus musculus (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
0.0000027
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
0.0000033
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
0.0000039
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
0.0000045
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
0.0000087
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-[6-(quinolin-8-yl)pyridazin-3-yl]benzene-1-sulfonamide
0.0000169
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
0.0000291
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
0.0000292
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(2-ethylphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
0.0000317
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
0.000034
-
pH and temperature not specified in the publication Mus musculus 3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
0.0000365
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(2-methoxyphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
0.00004
-
pH and temperature not specified in the publication Mus musculus 2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
0.0000472
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(isoquinolin-8-yl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
0.0000825
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
0.0001
-
brain enzyme, pH and temperature not specified in the publication Mus musculus 4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
0.000101
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-methylbenzene-1-sulfonamide
0.000118
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
0.000402
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
0.000546
-
brain enzyme, pH and temperature not specified in the publication Mus musculus N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
0.02
-
pH and temperature not specified in the publication Mus musculus 3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide

General Information

General Information Comment Organism
malfunction kynurenine monooxygenase (KMO) is the ideal target for an inhibitor because its inhibition is expected to reduce the toxic metabolites and increase kynurenic acid (KYNA), which is neuroprotective. KMO inhibitors can correct the 3-HK/KYNA unbalance Mus musculus
physiological function the kynurenine pathway (KP) is the major route for tryptophan metabolism in mammals. Several metabolites in the KP, however, are potentially toxic, particularly 3-hydroxykynurenine (3-HK) and quinolinic acid (QA). QA is an excitotoxic agonist at the NMDA receptor, and 3-HK and QA are reported to increase in Huntington's disease (HD) Mus musculus