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Literature summary for 1.6.5.2 extracted from

  • Reigan, P.; Colucci, M.A.; Siegel, D.; Chilloux, A.; Moody, C.J.; Ross, D.
    Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human pancreatic MIA PaCa-2 cancer cells (2007), Biochemistry, 46, 5941-5950.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione ES936, potent inhibitor of NQO1 activity and cell proliferation. Approximately 90% inhibition of enzyme activity after 4 h. Inactivation is dependent upon NADH Homo sapiens
5-methoxy-1,2-dimethyl-3-[(4-pyridinyloxy)methyl]indole-4,7-dione approximately 90% inhibition of enzyme activity after 4 h, and this inactivation is dependent upon NADH Homo sapiens
6-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione approximately 90% inhibition of enzyme activity after 4 h, and this inactivation is dependent upon NADH Homo sapiens
6-methoxy-1,2-dimethyl-3-[(4-pyridinyloxy)methyl]indole-4,7-dione approximately 90% inhibition of enzyme activity after 4 h, and this inactivation is dependent upon NADH Homo sapiens
6-methoxy-1,2-dimethyl-3-[(acetoxy)methyl]indole-4,7-dione approximately 90% inhibition of enzyme activity after 4 h, and this inactivation is dependent upon NADH Homo sapiens
additional information indolequinones with 4-nitrophenoxy, 4-pyridinyloxy, and acetoxy substituents at the (indol-3-yl)methyl position are NADH-dependent inhibitors of recombinant human NQO1, indicative of mechanism-based inhibition. However, those with hydroxy and phenoxy substituents are poor inhibitors of NQO1 enzyme activity, due to attenuated elimination of the leaving group. 4-pyridinyloxy and acetoxy compounds are potent inhibitors of NQO1 activity but relatively poor inhibitors of cell proliferation. Phenoxy compounds, which are not inhibitors of NQO1 enzymatic activity, demonstrate potent growth inhibition Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P15559
-
-

Purification (Commentary)

Purification (Comment) Organism
by affinity chromatography Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
MiaPaCa-2 cell
-
Homo sapiens
-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
800
-
purified enzyme Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5-methoxy-1,2-dimethyl-3-(hydroxymethyl)indole-4,7-dione + NADH is efficiently metabolized by NQO1 Homo sapiens ? + NAD+
-
?
5-methoxy-1,2-dimethyl-3-[(phenoxy)methyl]indole-4,7-dione + NADH inefficient indolequinone substrate Homo sapiens ? + NAD+
-
?
6-methoxy-1,2-dimethyl-3-(hydroxymethyl)indole-4,7-dione + NADH is efficiently metabolized by NQO1 Homo sapiens ? + NAD+
-
?
6-methoxy-1,2-dimethyl-3-[(phenoxy)methyl]indole-4,7-dione + NADH inefficient indolequinone substrate Homo sapiens ? + NAD+
-
?

Synonyms

Synonyms Comment Organism
DT-diaphorase
-
Homo sapiens
EC 1.6.99.2 formerly Homo sapiens
NAD(P)H:quinone oxidoreductase 1
-
Homo sapiens
NQO1
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD
-
Homo sapiens