Specific nNOS Inhibitors for the Therapy And Prevention Of Human Melanoma
AssigneesNorthwestern University, The Regents of the University of California
InventorsFrank L. Myskens, JR., Richard B. Silverman, Sun Yang, Haitao Ji, Fengtian Xue, Thomas L. Poulos
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Abstract
Methods for melanoma treatment and prevention with selective nitric oxide synthase inhibitor compounds and related pharmaceutical compositions, alone or in conjunction with one or more other melanoma therapies.
Claims20
A method of affecting a nitric oxide synthase, said method comprising administering a neuronal nitric oxide synthase with an effective amount of a compound selected from compounds of a formula
- wherein R1 is selected from H, halogen, alkyl, and substituted alkyl moieties;
- R2 is selected from H, alkyl, aryl, amino, hydroxy, substituted aryl and substituted alkyl moieties;
- Z is selected from NH, O, and NHCO;
- and R3 is selected from alkyl, substituted alkyl, hydroxyalkyl, substituted hydroxyalkyl, arylalkylaminoalkyl, substituted arylalkylaminoalkyl, arylalkyloxaalkyl, substituted arylalkyloxaalkyl;
- arylalkyl, substituted arylalkyl, arylalkylamidoalkyl, substituted arylalkylamidoalkyl, aminoalkyl, and substituted aminoalkyl moieties, said substituents selected from halo and haloalkyl moieties, and salts thereof,
- said compound administered to at least one of a human melanocyte and a human melanoma cell.
A method of affecting nitric oxide production in a human melanoma, said method comprising:
- providing a compound selected from compounds of a formula
- wherein R1 is selected from H, halogen, methyl and substituted methyl moieties;
- R2 is selected from H, alkyl and substituted alkyl moieties;
- Z is selected from O and NH;
- and R4 is selected from H, alkyl, substituted alkyl and halogen moieties, and salts thereof, and
- contacting a cellular medium comprising human melanoma cells, said contact selectively affecting neuronal nitric oxide synthase over inducible and endothelial synthase isoforms.
A method of affecting expression of neuronal nitric oxide synthase, said method comprising:
- providing a compound selected from compounds of a formula
- wherein R1 is selected from H, halogen, methyl and substituted methyl moieties;
- R2 is selected from H, alkyl and substituted alkyl moieties;
- Z is selected from O and NH;
- and R4 is selected from H, alkyl, substituted alkyl and halogen moieties, and salts thereof;
- and
- contacting said compound with a cellular medium comprising one of human melanocytes, melanoma cells and a combination thereof, said compound in an amount sufficient to inhibit induction of neuronal nitric oxide synthase expression.
Dependencies are inferred from the claim text.