Compositions and methods for inhibiting arginase activity
The disclosure relates to a novel class of compounds that exhibit activity inhibitory activity toward arginase, and pharmaceutical compositions comprising the compounds of the disclosure. Also provided herein are methods of treating cancer with the arginase inhibitors of the disclosure.
1. A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula (I*):
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is methyl; and
R 4 is H or (C 1 -C 6 )alkyl.
2. The method of claim 1 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein R 4 is (C 1 -C 6 )alkyl.
5. The method of claim 4 , wherein R 4 is methyl, ethyl, propyl, or isopropyl.
6. The method of claim 1 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
8. The method of claim 6 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
9. The method of claim 1 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
10. The method of claim 9 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
11. The method of claim 9 , wherein the compound has the structure of the following formula:
or a pharmaceutically acceptable salt thereof.
12. The method of claim 1 , wherein the patient has melanoma.
13. The method of claim 1 , wherein the patient has non-small cell lung cancer.
14. The method of claim 1 , wherein the patient has colorectal cancer.
15. The method of claim 1 , wherein the patient has bladder cancer.
16. The method of claim 1 , wherein the patient has gastric cancer.
17. The method of claim 1 , wherein the patient has head and neck cancer.
18. The method of claim 1 , wherein the patient has mesothelioma.
19. The method of claim 1 , wherein the patient has bile duct cancer.
20. The method of claim 1 , wherein the patient has ovarian cancer.
21. The method of claim 1 , wherein the patient has multiple myeloma.
22. The method of claim 1 , wherein the patient has endometrial cancer.
23. The method of claim 1 , wherein the patient has esophageal cancer.
24. The method of claim 1 , wherein the patient has a gastrointestinal carcinoid tumor.
25. The method of claim 1 , wherein the patient has a gastrointestinal stromal tumor (GIST).
26. The method of claim 1 , further comprising conjointly administering one or more additional chemotherapeutic agents, wherein the one or more additional chemotherapeutic agents is selected from ipilimumab, MGA012, nivolumab, pembrolizumab, pidilizumab, and epacadostat.
27. The method of claim 26 , wherein the additional chemotherapeutic agent is epacadostat.
28. The method of claim 8 , further comprising conjointly administering one or more additional chemotherapeutic agents, wherein the one or more additional chemotherapeutic agents is selected from ipilimumab, MGA012, nivolumab, pembrolizumab, pidilizumab, and epacadostat.
29. The method of claim 28 , wherein the additional chemotherapeutic agent is epacadostat.
30. The method of claim 26 , wherein the additional chemotherapeutic agent is ipilimumab.
31. The method of claim 26 , wherein the additional chemotherapeutic agent is MGA012.
32. The method of claim 26 , wherein the additional chemotherapeutic agent is nivolumab.
33. The method of claim 26 , wherein the additional chemotherapeutic agent is pembrolizumab.
34. The method of claim 26 , wherein the additional chemotherapeutic agent is pidilizumab.
35. The method of claim 28 , wherein the additional chemotherapeutic agent is ipilimumab.
36. The method of claim 28 , wherein the additional chemotherapeutic agent is MGA012.
37. The method of claim 28 , wherein the additional chemotherapeutic agent is nivolumab.
38. The method of claim 28 , wherein the additional chemotherapeutic agent is pembrolizumab.
39. The method of claim 28 , wherein the additional chemotherapeutic agent is pidilizumab.