Quinone oxidoreductase-2-mediated prodrug cancer therapy

Science Translational Medicine

Volumn 2, Issue 40, 2010, Pages

  Middleton, Mark R ^a   Knox, Richard ^b   Cattell, Emma ^a   Oppermann, Udo ^c   Midgley, Rachel ^d   Ali, Raghib ^d   Auton, Tim ^b   Agarwal, Roshan ^e   Anderson, David ^d   Sarker, Debashis ^e   Judson, Ian ^e   Osawa, Tsuyoshi ^f   Spanswick, Victoria J ^f   Davies, Scot ^g   Hartley, John A ^f   Kerr, David J ^d,h  

^a CHURCHILL HOSPITAL   (United Kingdom)

^b BTG   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d UNIVERSITY OF OXFORD   (United Kingdom)

^e ROYAL MARSDEN HOSPITAL   (United Kingdom)

^f UNIVERSITY COLLEGE LONDON   (United Kingdom)

^g IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^h SIDRA MEDICAL AND RESEARCH CENTER   (Qatar)

Author keywords

[No Author keywords available]

Indexed keywords

CARICOTAMIDE; OXIDOREDUCTASE; QUINONE OXIDOREDUCTASE 2; TRETAZICAR; UNCLASSIFIED DRUG; 5-(1-AZIRIDINYL)-2,4-DINITROBENZAMIDE; ANTINEOPLASTIC AGENT; AZIRIDINE DERIVATIVE; CROSS LINKING REAGENT; DNA; NRH - QUINONE OXIDOREDUCTASE2; NRH QUINONE OXIDOREDUCTASE2; PRODRUG; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE);

ADULT; AGED; ANIMAL CELL; ANOREXIA; ARTICLE; CANCER CHEMOTHERAPY; CHINESE HAMSTER; CLINICAL ARTICLE; COLORECTAL CANCER; CONTINUOUS INFUSION; CYTOTOXICITY; DEHYDRATION; DIARRHEA; DNA CROSS LINKING; DRUG BINDING; DRUG CLEARANCE; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG POTENTIATION; ENZYME ACTIVITY; ENZYME STRUCTURE; ESOPHAGUS CANCER; FATIGUE; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPERTRANSAMINASEMIA; HYPONATREMIA; HYPOPHOSPHATEMIA; IN VITRO STUDY; INFECTION; LUNG FIBROBLAST; LYMPHOCYTE; MALE; MAXIMUM TOLERATED DOSE; MELANOMA; MULTICENTER STUDY; NAUSEA; NONHUMAN; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; SIDE EFFECT; SOLID TUMOR; TUMOR BIOPSY; VOMITING; CELL DEATH; CHEMICAL STRUCTURE; CHEMISTRY; CLINICAL TRIAL; DRUG EFFECT; ENZYME ACTIVATION; METABOLISM; MIDDLE AGED; NEOPLASM; X RAY CRYSTALLOGRAPHY;

ADULT; AGED; ANTINEOPLASTIC AGENTS; AZIRIDINES; CELL DEATH; CROSS-LINKING REAGENTS; CRYSTALLOGRAPHY, X-RAY; DNA, NEOPLASM; ENZYME ACTIVATION; FEMALE; HUMANS; MALE; MIDDLE AGED; MODELS, MOLECULAR; NEOPLASMS; PRODRUGS; QUINONE REDUCTASES;

EID: 77955626777     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3000615     Document Type: Article

References (17)

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17. Acknowledgments: We thank the Experimental Cancer Medicine Centres at University College London, the Institute for Cancer Research, and Oxford for clinical trial support. Assistance in creation of Figure 1 by W. H. Lee and T. Krojer is gratefully acknowledged. Funding: Cancer Research UK grants PH1/088 and C2259/A9994, Protherics, and National Institute for Health Research Biomedical Research Centres at Oxford and Royal Marsden. The Structural Genomics Consortium is a registered charity (number 1097737) that receives funds from the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, Genome Canada through the Ontario Genomics Institute, GlaxoSmithKline, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Ontario Innovation Trust, the Ontario Ministry for Research and Innovation, Merck & Co. Inc., the Novartis Research Foundation, the Swedish Agency for Innovation Systems, the Swedish Foundation for Strategic Research, and the Wellcome Trust. Author contributions: M.R.M., I.J., D.J.K., and J.A.H. designed and performed the clinical trial; E.C., R.M., Ra.A., Ro.A., D.S., S.D., and T.A. contributed to the conduct of the clinical trial; U.O. performed structural analysis; D.A. performed pharmacokinetic analysis; V.J.S. performed Comet assays; R.K., D.J.K., and T.O. designed and performed preclinical experiments. All the authors contributed to the writing of the manuscript. Competing interests: R.K. and T.A. own stock in BTG, which owns the patent on CB1954 with EP0152R; T.A. has also worked as a consultant for the company. Accession numbers: The structural model is deposited at PDB with code 1ZX1. Trial EudraCT Number 2004-004784-30.