Wortmannin analogs and methods of using same in combination with chemotherapeutic agents
View Patent ↗Novel wortmannin analogs and their use in inhibiting PI-3-kinase activity in mammals and the treatment or prevention of cancer and tumor formation in a subject are described herein. Preferably, the wortmannin analogs may be administered with other chemotherapeutic agents in the treatment of cancer.
1. A method of treating cancer comprising administering to a subject a pharmaceutically effective amount of a compound selected from
wherein Y is a heteroatom selected from nitrogen and sulfur and R1 and R2 are independently selected from an unsaturated alkyl, non-linear alkyl, cyclic alkyl, and substituted alkyl, and a cancer chemotherapeutic agent.
2. The method of claim 1 , wherein said R1 and R2 are a disubstituted alkyl.
3. The method of claim 1 , wherein said cancer chemotherapeutic agent is selected from the group consisting of a cytotoxic agent and an anti-tumor targeting agent.
4. The method of claim 3 , wherein said cytotoxic agent is selected from the group consisting of gemeitabine, paclitaxel, and cisplatin.
5. The method of claim 3 , wherein said anti-tumor targeting agent is selected from the group consisting of gefitinib, erlotinib, trastuzumab, cetuximab and bevacizumab.
6. The method of claim 1 , wherein said compound is selected from:
7. The method of claim 1 , wherein said compound is:
8. The method of claim 1 , wherein said compound is:
9. The method of claim 1 , wherein said compound is administered orally.
10. The method of claim 1 , wherein said compound is administered intravenously.
11. The method of claim 1 , wherein said compound is
and said chemotherapeutic agent is gefitinib.
12. The method of claim 1 , wherein said compound is
and said chemotherapeutic agent is bevacizumab.
13. The method of claim 1 , wherein said compound is
and said chemotherapeutic agent is gefitinib.
14. The method of claim 1 , wherein said compound is
and said chemotherapeutic agent is bevacizumab.
15. The method of claim 1 , further comprising administering an antihyperglycemic agent.
16. A composition comprising a compound of the formula selected from
wherein Y is a heteroatom selected from nitrogen and sulfur and R1 and R2 are independently selected from an unsaturated alkyl, non-linear alkyl, cyclic alkyl, and substituted alkyl, and a cancer chemotherapeutic agent.
17. The composition of claim 16 , wherein said compound is
18. The composition of claim 16 , wherein said compound is
19. A method of treating cancer comprising administering to a subject a pharmaceutically effective amount of a compound selected from
wherein Y is a heteroatom selected from nitrogen and sulfur and R1 and R2 are indepdently selected from an unsaturated alkyl, non-linear alkyl, cyclic alkyl, and substituted alkyl, and radiation.
20. The method of claim 19 , wherein said R1 and R2 are a disubstituted alkyl.
21. The method of claim 19 , wherein said compound is selected from
22. The method of claim 19 , wherein said compound is:
23. The method of claim 19 , wherein said compound is:
24. The method of claim 19 , wherein said compound is administered orally.
25. The method of claim 19 , wherein said compound is administered intravenously.