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Literature summary extracted from

  • Colucci, M.A.; Reigan, P.; Siegel, D.; Chilloux, A.; Ross, D.; Moody, C.J.
    Synthesis and evaluation of 3-aryloxymethyl-1,2-dimethylindole-4,7-diones as mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1) activity (2007), J. Med. Chem., 50, 5780-5789.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.6.5.2 medicine series of indolequinones are synthesized and tested as inhibitors for NQO1 in pancreatic tumor cells, NQO1 inhibition does not correlate with growth inhibitory activity in MiaPaCa-2 cells Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.6.5.2 expressed in Escherichia coli Homo sapiens
1.6.5.2 expression in Escherichia coli Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.6.5.2 3-(2,4-difluorophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 3-(2-fluoro-4-nitrophenoxymethyl)-5-methoxy-1,2-dimethylindole-4,7-dione
-
 Homo sapiens
1.6.5.2 3-(2-fluoro-4-nitrophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 3-(4-aminophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 3-(4-cyanophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells; indolequinone derivative 22, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 3-(4-fluorophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione indolequinone derivative 24, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 3-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione
-
 Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(2,4,6-trifluorophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells; indolequinone derivative 10, mechanism based 80% inhibition Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(2-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(3-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCaa-2 cells; indolequinone derivative 6, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione indolequinone derivative 12, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione
-
 Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(pyridin-2-yloxymethyl)indole-4,7-dione indolequinone derivative 11, mechanism based 90% inhibition Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione
-
 Homo sapiens
1.6.5.2 5-methoxy-1,2-dimethyl-3-[1-(4-nitrophenoxy)ethyl]indole-4,7-dione
-
 Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(2,4,6-trifluorophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells; indolequinone derivative 26, mechanism based 90% inhibition Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(2-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCaa-2 cells Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(3-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells; indolequinone derivative 15, mechanism based 85% inhibition Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione
-
 Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(pyridin-2-yloxymethyl)indole-4,7-dione indolequinone derivative 27, mechanism based 90% inhibition Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione indolequinone derivative 29, mechanism based 95% inhibition Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-[2-nitrophenoxymethyl]indole-4,7-dione indolequinone derivative 19, mechanism based 95% inhibition, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 6-methoxy-1,2-dimethyl-3-[4-(trifluoromethyl)phenoxymethyl]-indole-4,7-dione effective inhibitor of the growth of MiaPaCa-2 cells; indolequinone derivative 23, dose dependent inhibition of NQO1 activity in MiaPaCa-2 Homo sapiens
1.6.5.2 additional information compounds 5-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione, 6-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione, 5-methoxy-1,2-dimethyl-3-(2,4-dinitrophenoxymethyl)indole-4,7-dione, 6-methoxy-1,2-dimethyl-3-(2,4-dinitrophenoxymethyl)indole-4,7-dione, 3-(2-fluoro-4-nitrophenoxymethyl)-5-methoxy-1,2-dimethylindole-4,7-dione, 3-(4-fluorophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione, 5-methoxy-1,2-dimethyl-3-(pyridin-2-yloxymethyl)indole-4,7-dione, 6-methoxy-1,2-dimethyl-3-(pyridin-2-yloxymethyl)indole-4,7-dione, 5-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione, 3-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione, 5-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione, 6-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione, and 5-methoxy-1,2-dimethyl-3-[1-(4-nitrophenoxy)ethyl]indole-4,7-dione are relatively ineffective at inducing growth inhibition. Inhibition of recombinant NQO1 is related to the pKa of the leaving group: compounds with poorer phenolic leaving groups are poor inhibitors whereas those with more acidic leaving groups are more efficient inhibitors Homo sapiens

Organism

EC Number Organism UniProt Comment Textmining
1.6.5.2 Homo sapiens
-
-
-
1.6.5.2 Homo sapiens
-
 recombinant protein
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.6.5.2 by affinity chromatography Homo sapiens
1.6.5.2 of the recombinant protein by cibacron blue affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
1.6.5.2 MiaPaCa-2 cell
-
 Homo sapiens
-
1.6.5.2 MiaPaCa-2 cell human pancreatic carcinoma cells Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.6.5.2 NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
-
 Homo sapiens NADP+ + reduced 2,6-dichlorophenolindophenol
-
 ?
1.6.5.2 NADPH + H+ + quinone
-
 Homo sapiens NADP+ + ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.6.5.2 EC 1.6.99.2 formerly Homo sapiens
1.6.5.2 NAD(P)H:quinone oxidoreductase 1
-
 Homo sapiens
1.6.5.2 NADPH:quinone oxidoreductase 1
-
 Homo sapiens
1.6.5.2 NQO1
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.6.5.2 0.000255
-
-
 Homo sapiens 3-(2,4-difluorophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.000345
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(2-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000351
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(3-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000352
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(3-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000363
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(2-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000427
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(2,4,6-trifluorophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000452
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(2,4,6-trifluorophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000463
-
-
 Homo sapiens 3-(4-cyanophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.000496
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-[4-(trifluoromethyl)phenoxymethyl]-indole-4,7-dione
1.6.5.2 0.000504
-
-
 Homo sapiens 3-(4-aminophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.000529
-
-
 Homo sapiens 3-(2-fluoro-4-nitrophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.000629
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000638
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(4-nitrophenoxymethyl)indole-4,7-dione
1.6.5.2 0.000904
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione
1.6.5.2 0.000905
-
-
 Homo sapiens 3-(4-fluorophenoxymethyl)-6-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.001385
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione
1.6.5.2 0.001829
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-[1-(4-nitrophenoxy)ethyl]indole-4,7-dione
1.6.5.2 0.002007
-
-
 Homo sapiens 5-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione
1.6.5.2 0.002475
-
-
 Homo sapiens 3-methoxy-1,2-dimethyl-3-(3-pyridyloxymethyl)indole-4,7-dione
1.6.5.2 0.00256
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(pyridin-4-yloxymethyl)indole-4,7-dione
1.6.5.2 0.004563
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(phenoxymethyl)indole-4,7-dione
1.6.5.2 0.004654
-
-
 Homo sapiens 3-(2-fluoro-4-nitrophenoxymethyl)-5-methoxy-1,2-dimethylindole-4,7-dione
1.6.5.2 0.009579
-
-
 Homo sapiens 6-methoxy-1,2-dimethyl-3-(pyridin-2-yloxymethyl)indole-4,7-dione