Compounds and methods of use
This disclosure provides compounds and compositions and methods of using those compounds and compositions to treat diseases and disorders associated with excessive transforming growth factor-beta (TGFβ) activity. This disclosure also provides methods of using the compounds in combination with one or more cancer immunotherapies.
1. A method of treating a tumor in an individual diagnosed with cancer, comprising administering to the individual an effective amount of
4-(2-(5-chloro-2-fluorophenyl)-5-isopropylpyridin-4-ylamino)-N-(1,3-dihydroxypropan-2-yl)nicotinamide or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from the group consisting of colon cancer, liver cancer, thyroid cancer, endometroid cancer, gallbladder cancer, kidney cancer, adrenocortical cancer, skin cancer, head and neck cancer and sarcoma.
2. The method of claim 1 , wherein the individual is diagnosed with colon cancer.
3. The method of claim 2 , wherein the colon cancer is selected from the group consisting of colon adenocarcinoma, colon adenocarcinoma from a metastatic site lymph node, metastatic colorectal cancer, and colon carcinoma.
4. The method of claim 1 , wherein the individual is diagnosed with liver cancer.
5. The method of claim 4 , wherein the liver cancer is selected from the group consisting of hepatocellular carcinoma, hepatoblastoma and cholangiocarcinoma.
6. The method of claim 1 , wherein the individual is diagnosed with thyroid cancer.
7. The method of claim 6 , wherein the thyroid cancer is selected from the group consisting of papillary thyroid carcinoma, follicular thyroid cancer and medullary thyroid cancer.
8. The method of claim 1 , wherein the cancer is endometroid cancer.
9. The method of claim 8 , wherein the endometrial cancer is selected from the group consisting of high grade endometroid cancer, uterine papillary serous carcinoma and uterine clear cell carcinoma.
10. The method of claim 1 , wherein the cancer is gallbladder cancer.
11. The method of claim 10 , wherein the gallbladder cancer is gallbladder adenocarcinoma or squamous cell gallbladder carcinoma.
12. The method of claim 1 , wherein the cancer is kidney cancer.
13. The method of claim 12 , wherein the kidney cancer is renal cell carcinoma or urothelial cell carcinoma.
14. The method of claim 1 , wherein the cancer is adrenocortical cancer.
15. The method of claim 14 , wherein the adrenocortical cancer is adrenal cortical carcinoma.
16. The method of claim 1 , wherein the cancer is skin cancer.
17. The method of claim 16 , wherein the skin cancer is selected from the group consisting of basal cell carcinoma, squamous carcinoma and melanoma.
18. The method of claim 1 , wherein the cancer is head and neck cancer.
19. The method of claim 18 , wherein the head and neck cancer is selected from the group consisting of oropharyngeal cancer, nasopharyngeal cancer, laryngeal cancer and cancer of the trachea.
20. The method of claim 1 , wherein the cancer is sarcoma.
21. The method of claim 20 , wherein the sarcoma is selected from the group consisting of synovial sarcoma, osteosarcoma, rhabdomiosarcoma, fibrosarcoma and Ewing's sarcoma.
22. The method of claim 1 , wherein the pharmaceutically acceptable salt is a hydrochloride salt.
23. The method of claim 1 , further comprising administering to the individual a second cancer therapy.
24. The method of claim 23 , wherein the second cancer therapy comprises a therapy selected from the group consisting of surgery, radiation, and chemotherapy.
25. A compound:
26. A compound: