Title:
FLAVIN N-OXIDES: NEW ANTI-CANCER AGENTS AND PATHOGEN ERADICATION AGENTS
Document Type and Number:
WIPO Patent Application WO2004043338
Kind Code:
A3
Abstract:
Compounds comprising flavin N-oxides for treatments of solid tumors, non-solid tumor masses, leukemias, and non-small cell lung cancers and for eradicating contaminants in blood products. Methods of treating patients having solid type cancers comprising administering a therapeutically effective amount of flavin N-oxide to a subject in need of treatment and exposing the flavin n-oxide to an activator such that activation of the flavin N-oxide results in damage to the DNA in the cancer cells without substantial damage to the DNA of normal cells are also provided. Methods of using a flavin N-oxide as part of a combination therapy with chemotherapy, radiation therapy, or both are also provided. methods of reducing pathogenic bacterial or rival contamination in a composition comprising a) mixing the composition with an efficacious amount of flavin N-oxide and b) exposing the mixture of the composition and the flavin N-oxide to an activator for a period of time sufficient to activate the flavin N-oxide such that the flavin N-oxide reduces the contamination in the composition are also provided. Preferably, the composition is a blood product selected from plasma, platelets, and red blood cells, and the activator is an enzyme.
Inventors:
PLATZ MATTHEW S (US)
Application Number:
PCT/US2003/014673
Publication Date:
March 24, 2005
Filing Date:
May 12, 2003
Export Citation:
Assignee:
UNIV OHIO STATE (US)
PLATZ MATTHEW S (US)
PLATZ MATTHEW S (US)
International Classes:
A61K31/525; A61K31/7056; A61K39/245; A61K41/00; A61K45/06; C07D475/14; C12N5/08; (IPC1-7): A61K31/50; A61K31/497; A61K31/501; C07H19/207
Foreign References:
| US6277377B1 | 2001-08-21 | |||
| US6258577B1 | 2001-07-10 | |||
| US5945420A | 1999-08-31 |
Other References:
FIESCHI ET AL.: "The mechanism and substrate specificity of the NADPH: Flavin oxidoreductase from escherichia coli", JOURNAL OF BIOCHEMICAL CHEMISTRY, vol. 270, no. 51, December 1995 (1995-12-01), pages 30392 - 30400, XP002982888
XUN ET AL.: "Characterization of 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, no. 2, February 2000 (2000-02-01), pages 481 - 486, XP002224426
NIVIERE ET AL.: "Is the NAD(P)H: flavin oxidoreductase from Escherichia coli a member of the ferredoxin-NADP+ reductase family?", vol. 271, no. 28, 12 July 1996 (1996-07-12), pages 16656 - 16661, XP002982889
NIVIERE ET AL.: "The NAD(P)H :flavin oxidoreductase from escherichia coli", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 26, June 1999 (1999-06-01), pages 18252 - 18260, XP002982890
WOODMANSEE ET AL.: "Reduced flavins promote oxidative DNA damage in non-respiring escherichia coli by delivering electrons to intracellular free iron", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277, no. 37, September 2002 (2002-09-01), pages 34055 - 34066, XP002982891
MUMTAZ KASIM: "The role of the N(5) interaction and association conformational changes in the modulation of the redox properties in flavoproteins", DISSERTATION, 1 January 2002 (2002-01-01), XP008042324
See also references of EP 1531823A4
XUN ET AL.: "Characterization of 4-hydroxyphenylacetate 3-hydroxylase (HpaB) of escherichia coli as a reduced flavin adenine dinucleotide-utilizing monooxygenase", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, no. 2, February 2000 (2000-02-01), pages 481 - 486, XP002224426
NIVIERE ET AL.: "Is the NAD(P)H: flavin oxidoreductase from Escherichia coli a member of the ferredoxin-NADP+ reductase family?", vol. 271, no. 28, 12 July 1996 (1996-07-12), pages 16656 - 16661, XP002982889
NIVIERE ET AL.: "The NAD(P)H :flavin oxidoreductase from escherichia coli", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 26, June 1999 (1999-06-01), pages 18252 - 18260, XP002982890
WOODMANSEE ET AL.: "Reduced flavins promote oxidative DNA damage in non-respiring escherichia coli by delivering electrons to intracellular free iron", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 277, no. 37, September 2002 (2002-09-01), pages 34055 - 34066, XP002982891
MUMTAZ KASIM: "The role of the N(5) interaction and association conformational changes in the modulation of the redox properties in flavoproteins", DISSERTATION, 1 January 2002 (2002-01-01), XP008042324
See also references of EP 1531823A4
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