PKM2 modulators and methods for their use
Compounds having activity as PKM2 activators are disclosed. The compounds have the following structure (I): including stereoisomers, tautomers, pharmaceutically acceptable salts and prodrugs thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
1. A method for increasing PKM2 activity in the provision of decreased tumorigenicity in a subject in need thereof, the method comprising:
administering an effective amount of a PKM2 activating compound in the form of a free-base or a pharmaceutically acceptable salt, or tautomer or prodrug thereof, to the subject, wherein said compound is:
2. The method of claim 1 , wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.
3. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.
4. The method of claim 3 , wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.
5. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.
6. The method of claim 5 , wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.
7. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.
8. The method of claim 7 , wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.
9. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt, tautomer, or prodrug thereof.
10. The method of claim 9 , wherein the tumorigenicity is due to lung cancer, pancreatic cancer, skin cancer, colon cancer, breast cancer, kidney cancer, ovarian cancer, or a hematological malignancy.
11. The method of claim 1 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.
12. The method of claim 3 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.
13. The method of claim 5 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.
14. The method of claim 7 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.
15. The method of claim 9 , further comprising administering an effective amount of one or more chemotherapeutic agents to the subject.
16. The method of claim 1 , wherein the compound is:
in the form of a free-base.
17. The method of claim 1 , wherein the compound is:
in the form of a pharmaceutically acceptable salt.