Dual targeting anticancer agents
Methods, compounds, and compositions for treating a proliferative disorder or other physiological conditions via a dual targeting anticancer therapy are provided. In some embodiments, a dual targeting anticancer therapy may utilize a composition comprising a platinum agent. The platinum agent may comprise a precursor to a therapeutically active platinum compound and at least one precursor to a vitamin E agent. The vitamin E agent may target cancer cells via a different mechanism of action than the therapeutically active platinum compound resulting in a dual targeting anticancer agent. The method of treatment may involve administering to a patient the dual targeting anticancer agent. Following administration, a therapeutically active platinum compound and a vitamin E agent may form at the physiologically relevant site. In some embodiments, administering a platinum agent comprising precursors of therapeutically active agents may be more effective than individually or simultaneously administering separate molecules of those therapeutically active agents.
1. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the vitamin E analog is tocotrienol or a tocotrienol analog.
2. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the vitamin E analog is of the formula:
3. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the vitamin E analog is of the formula:
4. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the vitamin E analog is of the formula:
5. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the vitamin E analog dissociates from the platinum center upon reduction of the platinum center.
6. A platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center and wherein the compound has the formula:
7. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 6 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
8. A method of treating cancer in a patient in need of treatment for cancer, comprising:
administering to the patient a platinum(IV) compound comprising at least one vitamin E analog, wherein the vitamin E analog is associated with the platinum center,
wherein, upon uptake of the composition into a cell, the platinum(IV) compound dissociates to form a therapeutically active platinum(II) compound and the vitamin E analog, and
wherein the cancer is lung cancer, cervical cancer, or ovarian cancer.
9. The method of claim 8 , wherein the cancer is cisplatin-resistant ovarian cancer.
10. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 1 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
11. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 2 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
12. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 3 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
13. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 4 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
14. A pharmaceutical composition, comprising:
a platinum(IV) compound as in claim 5 , or a pharmaceutically acceptable salt, thereof; and
one or more pharmaceutically acceptable carriers, additives and/or diluents.
15. The platinum(IV) compound of claim 3 , wherein the compound has the formula:
16. The platinum(IV) compound of claim 3 , wherein the compound has the formula:
17. The platinum(IV) compound of claim 2 , wherein the compound has the formula:
18. The platinum(IV) compound of claim 2 , wherein the compound has the formula: