Mitochondria-targeted anti-tumor agents
Described are mitochondria-targeted anti-tumor agents, and methods of making and using the same for the treatment of disorders associated with unwanted cell proliferation.
1. A composition comprising a compound consisting of a geldanamycin analogue covalently bonded to a linking moiety that is covalently bonded to (aryl) 3 P, wherein the linking moiety consists of an alkylene with six carbon atoms and the geldanamycin analogue is selected from the group of: 17-allylamino-demethoxygeldanamycin, 17-dimethylaminogeldanamycin, 17-(3-(4-maleimidobutyrcarboxamido) propylamino)-demethoxygeldanamycin, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin, 17-[2-(pyrrolidin-1-yl)ethyl]amino-17-demethmoxygeldanamycin,17-dimethylaminopropylamino)-17-demethoxygeldanamycin, and
wherein R 2 is H, alkyl, aryl, or arylalkyl; R 3 is H or alkyl; and R 4 is H, alkyl, aryl, arylalkyl, or OR d , wherein R d is H, alkyl, or arylalkyl; or a pharmaceutically acceptable salt of the compound.
2. The composition of claim 1 , wherein the geldanamycin analogue is 17-allylamino-demethoxygeldamycin (17-AAG).
3. The composition of claim 1 , wherein the geldanamycin analogue is 17-dimethylaminogeldanamycin.
4. The composition of claim 1 , wherein the geldanamycin analogue is
wherein:
R 2 is H, alkyl, aryl, or arylalkyl; R 3 is H or alkyl; and R 4 is H, alkyl, alkenyl, aryl, arylalkyl, or OR d , wherein R d is H, alkyl, or arylalkyl.
5. The composition of claim 4 , wherein R 2 is H or alkyl; R 3 is H or alkyl; and R 4 is H or OR d , wherein R d is H or alkyl.
6. The composition of claim 4 , wherein R 2 is H; R 3 is methyl; and R 4 is H.
7. The composition of claim 1 , wherein the compound is in the form of a pharmaceutically acceptable salt.
8. The composition of claim 1 , wherein the (aryl) 3 P is (phenyl) 3 P.
9. The composition of claim 1 , wherein the compound consists of:
10. A method for treating a subject having lung cancer, breast cancer, or prostate cancer, the method comprising administering to a subject having lung cancer, breast cancer, or prostate cancer a therapeutically effective amount of the composition of claim 1 .
11. A method for treating a subject having lung cancer, breast cancer, or prostate cancer, the method comprising:
identifying a subject having lung cancer, breast cancer, or prostate cancer; and
administering to the subject a therapeutically effective amount of the composition of claim 1 .
12. The method of claim 10 , wherein the subject has lung cancer.
13. The method of claim 10 , wherein the subject has breast cancer.
14. The method of claim 10 , wherein the subject has prostate cancer.
15. The method of claim 11 , wherein the subject is identified as having lung cancer.
16. The method of claim 11 , wherein the subject is identified as having breast cancer.
17. The method of claim 11 , wherein the subject is identified as having prostate cancer.
18. A method for treating a subject having lung cancer, breast cancer, or prostate cancer, the method comprising administering to a subject having lung cancer, breast cancer, or prostate cancer a therapeutically effective amount of a composition comprising a compound consisting of:
or a pharmaceutically acceptable salt of the compound.
19. The method of claim 18 , wherein the subject has lung cancer.
20. The method of claim 18 , wherein the subject has breast cancer.
21. The method of claim 18 , wherein the subject has prostate cancer.
22. The method of claim 11 , wherein the compound consists of:
23. The method of claim 22 , wherein the subject is identified as having lung cancer.
24. The method of claim 22 , wherein the subject is identified as having breast cancer.
25. The method of claim 22 , wherein the subject is identified as having prostate cancer.