Platinum (IV) complexes for use in dual mode pharmaceutical therapy
The present invention provides compositions, preparations, formulations, kits, and methods useful for treating subjects in need of therapeutic protocol, including subjects having cancer or at risk of developing cancer. Some embodiments of the invention may comprise a composition comprising a first component comprising a precursor to a therapeutically active platinum agent and a precursor to a second therapeutically active agent. The therapeutically active platinum agent and the second therapeutically active agent may dissociate from each other, thereby forming a first therapeutically active platinum agent and a second therapeutically active agent. The second therapeutically active gent may affect a cellular pathway of a cancer cell and may be substantially inactive towards non-cancerous cells.
1. A composition of matter, comprising:
a compound having the formula,
wherein:
R 1 , R 2 , R 3 , and R 4 can be the same or different and each is a group comprising at least one of ammonia, an amine, an aryl group, a heterocycle including at least one nitrogen, or a leaving group, any being optionally substituted, or, any two or three of R 1 , R 2 , R 3 and R 4 can be joine together to form a bidentate ligand or tridentate ligand, any being optionally substituted; and
R 5 and R 6 can be the same or different and at least one is a therapeutically active, or a precursor of a therapeutically active compound, when dissociated from the platinum, wherein the therapeutically active compound selectively affects a cellular pathway of a cancer cell and is substantially inactive toward non-cancerous cells, and wherein at least one of R 5 or R 6 comprises the group, —OC(O)(CHCl 2 ).
2. The composition of claim 1 , wherein each of R 5 and R 6 comprise the group, —OC(O)(CHCl 2 ).
3. The composition of claim 1 , wherein each of R 1 and R 2 comprise the group, NH 3 .
4. The composition of claim 1 , wherein the therapeutically active compound is dissociated from the platinum center upon reduction of the platinum center.
5. The composition of claim 1 , wherein the dissociation of R 5 and R 6 from the platinum center forms a compound having the formula,
6. The composition of claim 1 , wherein the composition, prior to uptake into a cell, is substantially therapeutically inactive.
7. The composition of claim 1 , wherein the at least one of R 5 or R 6 which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 800 g/mol.
8. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 600 g/mol.
9. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 400 g/mol.
10. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 300 g/mol.
11. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 200 g/mol.
12. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, has a molecular weight of less than about 100 g/mol.
13. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, is directly associated with platinum center.
14. The composition of claim 1 , wherein the at least one of R 5 or R 6 , which acts as a therapeutically active compound, or a precursor of a therapeutically active compound, when dissociated from platinum, is associated with platinum center through a tether.
15. The composition of claim 1 , wherein the therapeutically active compound is not a steroid.
16. The composition of claim 1 , wherein the therapeutically active compound causes at least a ten-fold increase in cell death in a cancer cell compared to a non-cancer cell.