Target Validation Information
Target ID T52389
Target Name NAD(P)H dehydrogenase [quinone] 1
Target Type
Clinical Trial
Drug Potency against Target NSC-106547 Drug Info IC50 = 10000 nM [528457]
NSC-354279 Drug Info IC50 = 2000 nM [528457]
NSC-2113 Drug Info IC50 = 3500 nM [528457]
Ethyl Bis(4-hydroxy-2-oxo-2H-chromen-3-yl)acetate Drug Info IC50 = 1221 nM [530490]
4-Hydroxy-3-(1-naphthylmethyl)-2H-chromen-2-one Drug Info IC50 = 1522 nM [530490]
3-Benzyl-4-hydroxy-2H-benzo[h]chromen-2-one Drug Info IC50 = 880 nM [530490]
4-amino-2H-chromen-2-one Drug Info IC50 = 13000 nM [529150]
NSC-106080 Drug Info IC50 = 3000 nM [531262]
NSC-99528 Drug Info IC50 = 1100 nM [531262]
Apaziquone Drug Info IC50 = 69 nM [552636]
NSC-645827 Drug Info IC50 = 700 nM [528457]
NSC-224124 Drug Info IC50 = 12500 nM [528457]
NSC-73410 Drug Info IC50 = 7500 nM [528457]
NSC-316158 Drug Info IC50 = 17500 nM [528457]
NSC-645808 Drug Info IC50 = 10000 nM [528457]
NSC-275420 Drug Info IC50 = 3000 nM [528457]
NSC-339580 Drug Info IC50 = 3000 nM [528457]
NSC-339583 Drug Info IC50 = 2000 nM [528457]
3-(3,4-Dimethylbenzyl)-4-hydroxy-2H-chromen-2-one Drug Info IC50 = 1600 nM [530490]
2-Benzyl-1-hydroxy-3H-benzo[f]chromen-3-one Drug Info IC50 = 465 nM [530490]
3-Benzyl-4-hydroxy-2H-chromen-2-one Drug Info IC50 = 3200 nM [530490]
4-Hydroxy-3-(2-naphthylmethyl)-2H-chromen-2-one Drug Info IC50 = 1452 nM [530490]
3-Benzyl-4-hydroxy-6,7-dimethyl-2H-chromen-2-one Drug Info IC50 = 660 nM [530490]
NSC-621351 Drug Info IC50 = 390 nM [531262]
NSC-65069 Drug Info IC50 = 10000 nM [531262]
Action against Disease Model Apaziquone EO-9 induces a broad spectr uM of activity (IC50 values range from 8 to 590 ng ml-1) against a panel of h uMan and murine t uMour cell lines. Some evidence exists of selectivitytowards leukaemia and h uMan colon cell lines as opposed to murine colon cells. The response of cells to Mitomycin C were not comparable to EO-9 suggesting that the mechanism of action of these compounds is different. The cytotoxic properties of EO-9 under aerobic conditions are significantly influenced by extracellular pH. Reduction of pH from 7.4 to 5.8 increases cell kill from 40% to 95% in DLD-1 cells [552477] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations Exposure of NQO1(-/-) mice to gamma-radiation led to myeloproliferative disease. Radiation-induced myeloproliferative disease was observed in 74% of NQO1(-/-) mice as compared with none in wild-type (WT) mice. NQO1(-/-) mice exposed to gamma-radiation also showed lymphoma tissues (32%) and lung adenocarcinoma (84%). In contrast, only 11% WT mice showed lymphoma and none showed lung adenocarcinoma. Exposure of NQO1(-/-) mice to gamma-radiation resulted in reduced apoptosis in granulocytes and lack of induction of p53, p21, and Bax. NQO1(-/-) mice also showed increased expression of myeloid differentiation factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and Pu.1. Intriguingly, exposure of NQO1(-/-) mice to gamma-radiation failed to induce C/EBPalpha and Pu.1,as was observed in WT mice. These results suggest that decreased p53/apoptosis and increased Pu.1 and C/EBPalpha led to myeloid hyperplasia in NQO1(-/-) mice [528457]
References
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 529150J Med Chem. 2007 Dec 13;50(25):6316-25. Epub 2007 Nov 14.Coumarin-based inhibitors of human NAD(P)H:quinone oxidoreductase-1. Identification, structure-activity, off-target effects and in vitro human pancreatic cancer toxicity.
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
Ref 552636Phase I/II pilot study of intravesical apaziquone (EO9) for superficial bladder cancer. J Urol. 2006 Oct;176(4 Pt 1):1344-8.
Ref 552477In vitro activity of the novel indoloquinone EO-9 and the influence of pH on cytotoxicity. Br J Cancer. 1992 Mar;65(3):359-64.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 528457Bioorg Med Chem Lett. 2006 Dec 15;16(24):6246-54. Epub 2006 Sep 29.In silico identification and biochemical characterization of novel inhibitors of NQO1.
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 530490J Med Chem. 2009 Nov 26;52(22):7142-56.Synthesis and biological evaluation of coumarin-based inhibitors of NAD(P)H: quinone oxidoreductase-1 (NQO1).
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).
Ref 531262Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6. Epub 2010 Oct 21.In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2).

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.