Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-12-03
2000-06-06
Goldberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514419, A61K 3140
Patent
active
060719494
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention is in the field of the prevention and treatment of cancer. More specifically, this invention relates to the use of 5-lipoxygenase inhibitors or derivatives thereof in preventing and treating cancer.
BACKGROUND OF THE INVENTION
Arachidonic acid (AA) is a 20-carbon polyunsaturated fatty acid derived from dietary sources. Oxygenated AA metabolites participate in a variety of biologic and pathological processes including inflammation, bronchial asthma, and shock. Activation of AA metabolism is initiated by the release of AA from the phospholipid pool by the action of enzymes or other mediators. The released AA can be metabolized by either the lipoxygenase pathway where AA is converted by fatty acid lipoxygenases into hydroperoxy derivatives, giving rise to leukotrienes, or the cycloxygenase pathway where a fatty acid transforms AA rapidly to the prostaglandin PGG.sub.2, which in turn is further converted enzymatically.
A protein designated 5-lipoxygenase activating protein (FLAP) appears to be necessary for cellular leuketriene synthesis (U.S. Pat. No. 5,182,367; Miller et al. (1990) Nature 343:278-281). FLAP appears to be involved in the translocation of 5-lipoxygenase from the cytosol to the membrane. Other enzymes involved with the sequential metabolism of the lipoxygenase product need to be in close relationship to the 5-lipoxygenase FLAP complex. FLAP and molecules of related structure may be essential to the activity of enzymes in the 5-lipoxygenase pathway as well as the other downstream enzymes required for leuketriene biosynthesis.
Inhibitors of the AA 5-lipoxygenase pathway have shown promise in the treatment of inflammation, asthma, and shock, with minimal side effects in pre-clinical and clinical trials (Batt, Prog. Med. Chem. 29:1-63 (1992); Larson, Ann. Pharmacother. 27:898-903 (1993)). However, their use for treating or preventing cancer has never been described.
The present invention is directed to the use of inhibitors of 5-lipoxygenase functional activity for the treatment and prevention of epithelial cell-derived cancers. The present invention is also directed to the use of inhibitors of other enzymes in the lipoxygenase pathway involved in the metabolism of AA for use in the treatment and prevention of epithelial cell-derived cancers.
SUMMARY OF THE INVENTION
In general the present invention relates to the use of lipoxygenase inhibitors in therapeutic applications, in particular to the prevention and treatment of epithelial cell-derived cancers.
It is an object of the present invention to provide a method for treating an epithelial cell-derived cancer in a subject in need of such treatment which comprises administering to the subject an inhibitor of a 5-lipoxygenase enzymatic function or a downstream leuketriene synthetic enzyme effective to treat the epithelial cell-derived cancer.
It is also an object of the present invention to provide a method for preventing an epithelial cell-derived cancer in a subject in need of such prevention which comprises administering to the subject an inhibitor of a 5-lipoxygenase enzymatic function or other downstream leuketriene synthetic enzyme effective to prevent the epithelial cell-derived cancer.
It is yet another object of the present invention to provide a method for preventing an epithelial cell-derived cancer in a subject in need of such prevention which comprises administering to the subject an amount of an inhibitor of an enzyme that metabolizes arachidonic acid effective to prevent an epithelial cell derived cancer.
It is a further object of the present invention to provide a method for treating an epithelial cell derived cancer in a subject in need of such treatment which comprises administering to the subject an amount of an inhibitor of an enzyme that metabolizes arachidonic acid effective to treat the epithelial cell-derived cancer.
It is also another object of the invention to provide a method for treating an epithelial cell derived cancer in a subject in need of such treatment which comprises adm
REFERENCES:
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patent: 5093351 (1992-03-01), Batt
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Carter et al. Chemotherapy of Cancer 2nd Ed John Wiley & Sons, N.Y., N.Y p. 364, 1981.
Jett Marti
Mulshine James L.
Auth Dorothy R.
Feiler William S.
Goldberg Jerome D.
The United States of America as represented by the Department of
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