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.
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Jiang L, Liu Y, Tumbath S, Boudreau MW, Chatkewitz LE, Wang J, Su X, Rafiq, Zahid K, Li K, Chen Y, Yang K, Hergenrother PJ, Huang X
Antioxid. Redox Signal. 2023, in press published on web November 11, 2023
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- Reactive Oxygen Species Synergize to Potently and Selectively Induce Cancer Cell Death
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ACS Chem. Biol. 2017, 12, 1416-1424
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- 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
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Invest New Drugs 2017, 35, 134-144
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ACS Chem. Biol. 2013, 8, 2173-2183.
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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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- Chemistry and Biology of Deoxynyboquinone, a Potent Inducer of Cancer Cell Death
Bair, J. S.; Palchaudhuri, R.; Hergenrother, P. J.
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