ACTIVATION BY NQO1

The enzyme NQO1 is typically a detoxification enzyme, catalyzing the reduction and elimination of exogenous and endogenous quinones. However, in 2012 we discovered that the action of NQO1 on the compound deoxynyboquinone (DNQ) results in reduction to the hydroquinone, followed by rapid conversion back to DNQ, and generating toxic reactive oxygen species in the process. As NQO1 is not appreciable expressed in normal tissue and is highly expressed in many solid tumors, DNQ rapidly and selectively generates ROS in tumor cells, and is very potent both in cell culture and in mouse models of cancer. DNQ and its derivatives have tremendous potential as potent and personalized anticancer agents.

 

 

Related Publications:

147. 

Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program

Janin M.; Ortiz-Barahona V.; Boudreau M.W.; Hergenrother P.J.; Esteller M. and others

Acta Neuropathol2019, published on web August 19, 2019

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125. 

Reactive Oxygen Species Synergize to Potently and Selectively Induce Cancer Cell Death

Lee, H.-Y.; Parkinson, E. I.; Granchi, C.; Paterni, I.; Panigrahy, D.; Seth, P.; Minutolo, F.; Hergenrother, P. J.

ACS Chem. Biol. 2017, 12, 1416-1424.

 

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124. 

Pharmacokinetics and Derivation of an Anticancer Dosing Regimen for the Novel Anti-Cancer Agent Isobutyl-Deoxynyboquinone (IB-DNQ), a NQO1 Bioactivatable Molecule, in the Domestic Felid Species

Lundberg, A. P.; Francis, J. M.; Pajak, M.; Parkinson, E. I.; Wycislo, K. L.; Rosol, T. J.; Brown, M. E.; London, C. A.; Dirikolu, L.; Hergenrother, P. J.; Fan. T. M.

Invest New Drugs 2017, 35, 134-144.

 

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115.

Deoxynyboquinones as NQO1-Activated Cancer Therapeutics

Parkinson, E. I.; Hergenrother, P. J.

Acc. Chem. Res. 2015, 48, 2715-2733.

 

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97.

Efficient NQO1 Substrates are Potent and Selective Anticancer Agents

Parkinson, E. I.; Bair, J. S.; Cismesia, M.; Hergenrother, P. J.

ACS Chem. Biol. 2013, 8, 2173-2183.

 

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Meet the Authors

90.

An NQO1 Substrate with Potent Anti-Tumor Activity that Selectively Kills by PARP-1-Induced Programmed Necrosis

Huang, X.; Dong, Y.; Bey, E. A.; Kilgore, J. A.; Bair, J. S.; Li, L.-S.; Patel, M.; Parkinson, E. I.; Wang, Y.; Williams, N. S.; Gao, J.; Hergenrother, P. J.; Boothman, D. A.

Cancer Res. 2012, 72, 3038-3047.

 

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69.

Chemistry and Biology of Deoxynyboquinone, a Potent Inducer of Cancer Cell Death

Bair, J. S.; Palchaudhuri, R.; Hergenrother, P. J.

J. Am. Chem. Soc. 2010, 132, 5469-5478.

 

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Professor Paul J. Hergenrother

hergenro@illinois.edu

261 Roger Adams Lab

600 S. Mathews Avenue

Urbana, IL 61802

The Chemistry Department at the University of Illinois

Copyright © 2014 The Hergenrother Group

Kate Neef

Administrative Assistant

kneef1@illinois.edu

245 Roger Adams Lab

#PJHteam