Kinase protein binding inhibitors
View Patent ↗The invention relates to phosphorylation inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating cell proliferative disorders, especially cancer.
1. A method of inducing apoptosis in a cancer cell that expresses FAK in a subject comprising administering to the subject identified as in need thereof a compound capable of inhibiting Y397 phosphorylation of FAK;
wherein the compound is:
Y15: 1, 2, 4, 5-benzenetetraamine tetrahydrochloride.
2. The method of claim 1 , wherein compound is capable of decreasing Y397-FAK phosphorylation in tumors.
3. The method of claim 2 , wherein the compound decreases FAK autophosphorylation in vitro.
4. The method of claim 2 , wherein the compound decreases FAK autophosphorylation in vivo.
5. The method of claim 4 , wherein the compound has an inhibiting effect on FAK autophosphorylation at least 2 times greater than its inhibiting effect on other kinases.
6. The method of claim 5 , wherein the kinase is IGFR-1, MAPK, or AKT.
7. The method of claim 2 , wherein the cancer is breast, colon, pancreatic, thyroid, lung, or melanoma.
8. A method of inhibiting a FAK phosphorylation in a subject identified as in need of such treatment, comprising administering a compound identified as capable of inhibiting Y397 phosphorylation of FAK;
wherein the compound is:
Y15: 1, 2, 4, 5-benzenetetraamine tetrahydrochioride.
9. A method of treating cancer that expresses FAK in a subject comprising administering to the subject identified as in need thereof a compound capable of inhibiting Y397 phosphorylation of FAK;
wherein the compound is:
Y15: 1, 2, 4 5-benzenetetraamine tetrahydrochioride.
10. The method of claim 9 , wherein the inhibiting Y397 phosphorylation of FAK results in modulation of apoptosis or cellular proliferation of cancer cells.
11. The method of claim 9 , wherein the cancer is breast, colon, pancreatic, thyroid, lung, or melanoma.
12. A method of treating cancer that expresses FAK in a subject comprising administering to the subject a compound identified as capable of inhibiting Y397 phosphorylation of FAK and an additional therapeutic agent;
wherein the compound is:
Y15: 1, 2, 4, 5-benzenetetraamine tetrahydrochloride.
13. The method of claim 12 , wherein the cancer is breast, colon, pancreatic, thyroid, lung, or melanoma.
14. The method of claim 12 , wherein the compound identified as capable of inhibiting Y397 phosphorylation of FAK is 1, 2, 4, 5-benzenetetraamine tetrahydrochloride and the additional therapeutic agent is gemcitabine.