Agonists of EPHA and their uses
A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule having a general formula: A-L-X-Z (I).
1. A method of treating cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule having general formula:
wherein Z is a phenyl group substituted with at least one of an aryl,
wherein R 3 and R 4 are each individually selected from H, halogen, C 1-6 alkyl, C 1-6 aralkyl, C 1-6 heterocyclylalkyl, and C 1-6 carbocyclylalkyl, and pharmaceutically acceptable salts thereof; and wherein the cancer is a breast cancer, prostate cancer or glioma characterized by the overexpression of EphA2 receptor in cancer cells of the subject.
2. The method of claim 1 , the small molecule agonist of EphA2 receptor protein having the formula:
wherein R 3 is selected from H, halogen, C 1-6 alkyl, C 1-6 aralkyl, C 1-6 heterocyclylalkyl, and C 1-6 carbocyclylalkyl.
3. The method of claim 1 the small molecule agonist of EphA2 receptor protein having the formula:
wherein R 4 is selected from H, halogen, C 1-6 alkyl, C 1-6 aralkyl, C 1-6 heterocyclylalkyl, and C 1-6 carbocyclylalkyl.
4. The method of claim 1 , the small molecule agonist of EphA2 receptor protein selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
5. The method of claim 1 , wherein the small molecule agonist of EphA2 receptor protein is not doxazosin.
6. The method of claim 1 , the small molecule agonist of EphA2 receptor having a lower a-adrenoreceptor binding affinity than doxazosin.
7. The method of claim 1 , wherein the therapeutically effective amount of a small molecule agonist of EphA2 receptor is the amount effective to inhibit tumor growth associated with EphA2 tumorgenesis in the subject.
8. The method of claim 1 , wherein the therapeutically effective amount of a small molecule agonist of EphA2 receptor is the amount effective to activate and internalize EphA2 receptors in cancer cells of the subject.
9. The method of claim 1 , wherein the cancer is breast caner.
10. A method of treating cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule having the formula:
or a pharmaceutically acceptable salt thereof, wherein the cancer is a breast cancer, prostate cancer or glioma characterized by the overexpression of EphA2 receptor in cancer cells of the subject.
11. A method of treating cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule having the formula:
or a pharmaceutically acceptable salt thereof; and wherein the cancer is a breast cancer, prostate cancer or glioma characterized by the overexpression of EphA2 receptor in cancer cells of the subject.
12. A method of treating breast cancer in a subject, comprising:
administering to the subject a therapeutically effective amount of a small molecule agonist of EphA2 receptor protein, the small molecule agonist of EphA2 receptor protein selected from the group consisting of:
or a pharmaceutically acceptable salt thereof, wherein the breast cancer is characterized by the overexpression of EphA2 receptor in cancer cells of the subject.