HERGENROTHER LAB
Using small molecules to define new targets for the treatment of disease
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 Neuropathol. 2019, published on web August 19, 2019
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.
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.
115.
Deoxynyboquinones as NQO1-Activated Cancer Therapeutics
Parkinson, E. I.; Hergenrother, P. J.
Acc. Chem. Res. 2015, 48, 2715-2733.
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.
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.
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.