Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1999-05-24
2000-12-05
Stockton, Laura L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
548963, A61K 31396, C07D40302, C07D40308
Patent
active
061567442
ABSTRACT:
The present invention relates to a novel benzoquinone, 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone and its esters. The compounds can be used to treat tumors exhibiting elevated levels of the enzyme DT-diaphorase.
REFERENCES:
Winski et al.; Dec. 1998, "A New Screening System for NAD(P)H: Quinone Oxidoreductase (NQO1)-directed Antitumor Quinones: Identification of a New Aziridinylbenzoquinone, RH1, as a NQO1-directed Antitumor Agent" Clincal Cancer Research, 4:3083-3088.
Smitskamp-Wilms, E. et al; DT-diaphorase activity in normal and neoplastic human tissues; an indicator for sensitivity to bioreductive agents; Br.J. Cancer, 72:917-921,(1995).
Gibson, N.W., et al; Relationship between DT-diaphorase mediated metabolism of a series of aziridinylbenzoquinones and DNA damage and cytotoxicity; Mol. Pharmocol., 42:531-536, (1992).
Lee, C.-S., et al; Alteration in DNA cross-linking and sequenec selectivity of a series of aziridinylbenzoquinones after enzymatic reduction by DT-diaphorase; Biochemistry, 31:3019-3025, (1992).
Fitzsimmons, S.A., et al; Reductase enzyme expression ascross the National Cancer Institute tumor cell line panel: Correlation with sensitivity to mitomycin C and EO9; JNCI, 88:259-269, (1996).
Phillips, R.M., et al; Increased activity and expression of NAD(P)H:quinone acceptor oxidoreductase in confluent cell cultures and within multicellular spheroids. Cancer Res., 54:3766-3771, (1994).
Traver, R.D., et al, Characterization of a polymorphism in NAD(P)H: Quinone oxidoreductase (DT-diaphorase), Br. J. Cancer, 75:69-75, 1997).
Gustafson, D. L., et al, Expression of human NQO1 (DT-diaphorase) in chinese hamster ovary cells: Effects on the toxicity of antitumor quinones; Mol. Pharmacol., 502:728-735, (1996).
Cummings, J., et al, Antitumor Activity of the Novel Bioreductive MeDZQ Against Human Non-Small Cell Lung Cancer Xenorgrafts; submitted to the 9th NCI-EORTC Symposium on New Drugs in Cancer Therapy, Amsterdam, The Netherlands, (Mar., 1996).
Beall, H.D., et al, Nicotinamide adenine dinucleotide (phosphate):quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: Quinone cytotoxicity and selectivity in human lung and breast cancer cell lines, Mol.Pharmacol., 48:499-504, (1995).
Ross, D. et al, DT-diaphorase in activation and detoxification of quinones, Cancer and Metastasis Reviews, 12:83-101, (1993).
Schlager, J., et al., Cytosolic NAD(P)H:(Quinone-Acceptor)Oxidoreductase in Human Normal and Tumor Tissue: Effects of Cigarette Smoking and Alcohol, Int. J. Cancer, 45: 403-409, (1990).
Berger, M., et al., Use of Quinones in Brain Tumor Therapy: Preliminary Results of Preclinical Laboratory Investigations, J. of Toxicology and Environmental Health, 16:713-719, (1985).
Xu, B.H., et al, Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue, British J.of Cancer, 69:242-246, (1994).
Malkinson, A., et al, Elevated DT-diaphorase Activity and Messenger RNA Content in Human Non-Small Lung Carcinoma: Relationship to the Response of Lung Tumor Xenografts to Mitomycin C, Cancer Research, 52: 4752-4757 (1992).
Spain, R., The Case for Mitomycin in Non-Small Cell Lung Cancer, Oncology (1993); 50:(suppl 1):35-52.
Beall, H. et al., Metabolism of Bioreductive Antitumor Compounds by Purified Rat and Human DT-Diaphorases, Cancer Research, 54:3196-3201, (1994).
Siegel, D., et al, pH Dependent Inactivation of DT-Diaphorase by Mitomycin C and Porfiromycin, Molecular Pharmacology, 44:1128-1134, (1993).
Ross, D., et al., Bioactivation of Quinones by DT-diaphorase, Molecular, Biochemical, and Chemical Studies; Oncology Research, vol. 6, Nos. 10/11: 493-500, (1994).
Kepa, J.K., et al., Comparison of human NQ01 promoter activity in NSCLC and SCLC cell lines. Proc. Am. Assoc. Cancer Res., 38:2515, (1997). Abstract.
Kelsey, K.T., et al, Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductace polymorphism and its implications for anti-cancer chemotherapy, British J. of Cancer, 76(7): 852-854, (1997).
Beall Howard D.
Butler John
Hargreaves Robert H. J.
Ross David
Siegel David
Cancer Research Campaign Tech (London)
Stockton Laura L.
University of Salford
University Technology Corp.
LandOfFree
DT-diaphorase directed anti-tumor agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with DT-diaphorase directed anti-tumor agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and DT-diaphorase directed anti-tumor agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-961878