Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.6.5.2 (
NQO1
)
6,196
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
NAD(P)H quinone oxidoreductase (
NQO1
) has multiple functions in the cell including an ability to act as a detoxifying enzyme and as a protein chaperone. The latter property is particularly important in oncology as one of the client proteins of
NQO1
is p53. The inhibitor, dicoumarol, is classically used to probe the biological properties of
NQO1
, but interpretation of enzyme function is compromised by the multiple "off-target" effects of this agent. Coumarin-based compounds that are more potent than dicoumarol as inhibitors of recombinant human
NQO1
have been identified (Nolan et al., J Med Chem 2009;52:7142-56) The purpose of the work reported here is to demonstrate the functional activity of these agents for inhibiting
NQO1
in cells. To do this, advantage was taken of the
NQO1
-mediated toxicity of the chemotherapeutic drug EO9 (
Apaziquone
). The toxicity of this drug is substantially reduced when the function of
NQO1
is inhibited and many of the coumarin-based compounds are more efficient than dicoumarol for inhibiting EO9 toxicity. The ability to do this appears to be related to their capacity to inhibit
NQO1
in cell free systems. In conclusion, agents have been identified that may be more pharmacologically useful than dicoumarol for probing the function of
NQO1
in cells and tissues.
...
PMID:Pharmacological inhibitors of NAD(P)H quinone oxidoreductase, NQO1: structure/activity relationships and functional activity in tumour cells. 2059 3
