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Literature summary for 1.13.11.11 extracted from

  • Wu, J.S.; Lin, S.Y.; Liao, F.Y.; Hsiao, W.C.; Lee, L.C.; Peng, Y.H.; Hsieh, C.L.; Wu, M.H.; Song, J.S.; Yueh, A.; Chen, C.H.; Yeh, S.H.; Liu, C.Y.; Lin, S.Y.; Yeh, T.K.; Hsu, J.T.; Shih, C.; Ueng, S.H.; Hung, M.S.; Wu, S.Y.
    Identification of substituted naphthotriazolediones as novel tryptophan 2,3-dioxygenase (TDO) inhibitors through structure-based virtual screening (2015), J. Med. Chem., 58, 7807-7819 .
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is a target for drug development Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene TDO2, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
1-(2-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(3-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(3-chlorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(3-[(4-acetyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(3-[(4-methyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(4-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(4-fluorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(4-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(4-[(4-acetylpiperazin-1-yl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-(4-[(4-methoxypiperidin-1-yl)carbonyl]benzyl)-1Hnaphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-[(3-methylphenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-[(4-chlorophenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
1-[3-(4-morpholinylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
-
Homo sapiens
1-[4-(morpholin-4-ylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
-
Homo sapiens
1-[4-[(4-methylpiperazin-1-yl)carbonyl]benzyl]-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
Homo sapiens
2-(4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]-triazol-1-yl)methyl]phenyl)-N,N-diethylacetamide
-
Homo sapiens
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
-
Homo sapiens
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
-
Homo sapiens
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
-
Homo sapiens
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
-
Homo sapiens
additional information identification of substituted naphthotriazolediones as tryptophan 2,3-dioxygenase (TDO) inhibitors through structure-based virtual screening, homology modeling and virtual screening, ligand docking analysis, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-tryptophan + O2 Homo sapiens
-
N-formyl-L-kynurenine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P48775
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Homo sapiens
-
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-tryptophan + O2
-
Homo sapiens N-formyl-L-kynurenine
-
?

Synonyms

Synonyms Comment Organism
TDO
-
Homo sapiens
TDO2
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
assay at Homo sapiens

Cofactor

Cofactor Comment Organism Structure
heme
-
Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00003
-
pH 8.0, 37°C Homo sapiens 1-(3-[(4-methyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
0.000048
-
pH 8.0, 37°C Homo sapiens 1-[3-(4-morpholinylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
0.000059
-
pH 8.0, 37°C Homo sapiens 1-(3-[(4-acetyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
0.00009
-
pH 8.0, 37°C Homo sapiens 3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
0.000108
-
pH 8.0, 37°C Homo sapiens 1-[4-[(4-methylpiperazin-1-yl)carbonyl]benzyl]-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
0.000116
-
pH 8.0, 37°C Homo sapiens 1-[4-(morpholin-4-ylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
0.000145
-
pH 8.0, 37°C Homo sapiens 2-(4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]-triazol-1-yl)methyl]phenyl)-N,N-diethylacetamide
0.000167
-
pH 8.0, 37°C Homo sapiens 3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
0.000176
-
pH 8.0, 37°C Homo sapiens 1-(4-[(4-acetylpiperazin-1-yl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
0.000181
-
pH 8.0, 37°C Homo sapiens 4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
0.000209
-
pH 8.0, 37°C Homo sapiens 1-(4-[(4-methoxypiperidin-1-yl)carbonyl]benzyl)-1Hnaphtho[2,3-d][1,2,3]triazole-4,9-dione
0.000312
-
pH 8.0, 37°C Homo sapiens 4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
0.000561
-
pH 8.0, 37°C Homo sapiens 1-(2-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.000711
-
pH 8.0, 37°C Homo sapiens 1-(3-chlorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.000768
-
pH 8.0, 37°C Homo sapiens 1-(3-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.001088
-
pH 8.0, 37°C Homo sapiens 1-(4-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.001586
-
pH 8.0, 37°C Homo sapiens 1-(4-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.001745
-
pH 8.0, 37°C Homo sapiens 1-[(3-methylphenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.00646
-
pH 8.0, 37°C Homo sapiens 1-[(4-chlorophenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
0.00738
-
pH 8.0, 37°C Homo sapiens 1-(4-fluorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione

General Information

General Information Comment Organism
metabolism the first and rate limiting step of the kynurenine pathway is carried out by two heme-containing enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52), which differ in their tissue distribution and regulation Homo sapiens
additional information TDO homology modeling, overview Homo sapiens
physiological function the enzyme is involved in L-tryptophan catabolism to produce bioactive metabolites including kynurenine, kynurenic acid, quinolinic acid, and the coenzyme NAD+ via the kynurenine pathway Homo sapiens