Methods of use of cyclopamine analogs
The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula:
1. A method for antagonizing the hedgehog pathway in a mammal comprising administering to the mammal a compound of the formula:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the compound is a hydrochloride salt.
4. A method for treating cancer in a mammal comprising administering to the mammal a compound of formula:
or a pharmaceutically acceptable salt thereof;
wherein said cancer is selected from the group consisting of basal cell carcinoma, glioma, breast cancer, chondrosarcoma, colon cancer, esophageal cancer, gastric cancer, gastrointestinal stromal tumor, hepatocellular cancer, lung cancer, medulloblastoma, melanoma, neuroectodermal tumors, osteogenic sarcoma, ovarian cancer, pancreatic cancer, prostate cancer, and testicular cancer.
5. The method of claim 4 , wherein the cancer is basal cell carcinoma, pancreatic cancer, prostate cancer, osteogenic sarcoma, chondrosarcoma, gastric cancer, esophageal cancer, lung cancer, glioma, breast cancer, hepatocellular cancer, ovarian cancer, colon cancer or medulloblastoma.
6. The method of claim 4 , wherein the cancer is pancreatic cancer.
7. The method of claim 4 , wherein the cancer is chondrosarcoma.
8. The method of claim 4 , wherein the cancer is lung cancer.
9. The method of claim 8 , wherein the lung cancer is small cell lung cancer.
10. The method of claim 4 , wherein the cancer is basal cell carcinoma.
11. The method of claim 4 , wherein the cancer is medulloblastoma.
12. The method of claim 4 , wherein the cancer is ovarian cancer.
13. The method of claim 4 , wherein the cancer is osteogenic sarcoma.
14. The method of claim 4 , wherein the compound is used in combination with one or more chemotherapeutic or other anti-cancer agent.
15. The method of claim 14 , wherein the other anti-cancer agent is radiation.
16. The method of claim 4 , wherein the compound is administered locally to a tumor.
17. The method of claim 4 , wherein the compound is administered systemically.
18. The method of claim 4 , wherein the mode of administration of said compound is inhalation, oral, intravenous, sublingual, ocular, transdermal, rectal, vaginal, topical, intramuscular, intraperitoneal, epidural, subcutaneous, buccal, or nasal.
19. The method claim 18 , wherein the mode of administration is oral, intravenous, or topical.
20. The method of claim 4 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.
21. The method of claim 20 , wherein the compound is a hydrochloride salt.