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Literature summary 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

EC Number Inhibitors Comment Organism Structure
1.14.13.9 (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
-
 Mus musculus
1.14.13.9 2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid PNU-168754 Mus musculus
1.14.13.9 3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide Ro-61-8048 Mus musculus
1.14.13.9 3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide JM-6 Mus musculus
1.14.13.9 3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid GSK-065 Mus musculus
1.14.13.9 3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 4-methyl-N-[6-(quinolin-8-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid CHDI-340246 Mus musculus
1.14.13.9 CHDI-340246
-
 Mus musculus
1.14.13.9 additional information synthesis and evaluation of enzyme inhibitors Mus musculus
1.14.13.9 N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(2-ethylphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(2-methoxyphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-methylbenzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-2-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-3-sulfonamide
-
 Mus musculus
1.14.13.9 N-[6-(isoquinolin-8-yl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
 Mus musculus

Localization

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

Natural Substrates/ Products (Substrates)

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

Organism

EC Number Organism UniProt Comment Textmining
1.14.13.9 Mus musculus Q91WN4
-
-
1.14.13.9 Mus musculus R6/2 Q91WN4
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.14.13.9 brain
-
 Mus musculus
-
1.14.13.9 liver
-
 Mus musculus
-

Substrates and Products (Substrate)

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

Synonyms

EC Number Synonyms Comment Organism
1.14.13.9 KMO
-
 Mus musculus
1.14.13.9 kynurenine monooxygenase
-
 Mus musculus

Cofactor

EC Number Cofactor Comment Organism Structure
1.14.13.9 FAD
-
 Mus musculus
1.14.13.9 NADPH
-
 Mus musculus

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.14.13.9 0.0000005
-
 pH and temperature not specified in the publication Mus musculus 6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 0.00004
-
 pH and temperature not specified in the publication Mus musculus 2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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
1.14.13.9 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

EC Number General Information Comment Organism
1.14.13.9 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
1.14.13.9 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