Anti-cancer compounds targeting Ral GTPases and methods of using the same
Methods of inhibiting the growth or metastasis of a cancer in a subject by inhibiting a Ral GTPase in the subject, and small molecule inhibitors of Ral GTPases useful in the methods of the invention. Pharmaceutical compositions containing the compounds of the invention, and methods of using the same.
1. A compound having a chemical structure selected from the group consisting of:
6-amino-1,3-dimethyl-4-(4-(trifluoromethyl)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile,
6-amino-1-methyl-3-phenyl-4-(4-(trifluoromethoxy)phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile,
6-amino-4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3-dimethyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile, and,
6-amino-3,4-bis(4-methoxyphenyl)-1-phenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile and pharmaceutically acceptable enantiomers, diastereomers, racemates, or salts thereof.
2. A pharmaceutical composition comprising at least one compound of claim 1 and at least one pharmaceutical excipient.
3. A method of treating, ameliorating cancer or preventing metastasis of a cancer in a subject comprising administering a therapeutically-effective amount of a compound of claim 1 that inhibits a Ral GTPase to a subject in need thereof.
4. The method of claim 3 , wherein the compound is administered to the subject within a pharmaceutical composition.
5. The method of claim 4 , wherein the pharmaceutical composition is a mono-phasic pharmaceutical composition suitable for parenteral or oral administration consisting essentially of a therapeutically-effective amount of the compound, and a pharmaceutically acceptable carrier.
6. The method of claim 4 , wherein the pharmaceutical composition is administered in conjunction with one or more geranylgeranyltransferase type I (GGTase-I) inhibitors, surgery, chemotherapy, radiation, immunotherapy, or combinations thereof.
7. A compound having a chemical structure selected from the group consisting of:
and
pharmaceutically acceptable enantiomers, diastereomers, racemates, or salts thereof.
8. A method of treating, ameliorating cancer or preventing metastasis of a cancer in a subject comprising administering a therapeutically-effective amount of a compound that inhibits a Ral GTPase to a subject in need thereof, wherein the compound has a chemical structure selected from:
and
pharmaceutically acceptable enantiomers, diastereomers, racemates, or salts thereof.