Composition and methods for the treatment of myelodysplastic syndrome and acute myeloid leukemia
Methods and compositions are provided for treating myelodysplastic syndrome and acute myeloid leukemia, wherein the composition comprises at least one compound according to Formula I: wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound; and a DNA methyltransferase inhibitor, or a pharmaceutically acceptable salt thereof.
1. A method of treating an individual for myelodysplastic syndrome or acute myeloid leukemia, comprising administering to the individual in need of such treatment, an effective amount of a composition comprising at least one compound according to Formula I:
wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound, and at least one DNA methyltransferase inhibitor selected from the group consisting of azacitidine, procaine, procainamide and epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
2. A method of treating an individual for myelodysplastic syndrome or acute myeloid leukemia, comprising administering to the individual in need of such treatment, an effective amount of at least one compound according to Formula I:
wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound, and at least one DNA methyltransferase inhibitor selected from the group consisting of azacitidine, procaine, procainamide and epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the at least one DNA methyltransferase inhibitor is procaine or procainamide, or a pharmaceutically acceptable salt thereof.
4. The method of claim 2 , wherein the at least one DNA methyltransferase inhibitor is epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
5. The method of claim 2 , wherein the at least one DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof.
6. The method of claim 2 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid, or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt.
8. The method of claim 7 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt and the DNA methyltransferase inhibitor is azacitidine.
9. The method of claim 1 , wherein the at least one DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid, or a pharmaceutically acceptable salt thereof.
11. The method of claim 10 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt.
12. The method of claim 11 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt and the DNA methyltransferase inhibitor is azacitidine.
13. The method of claim 2 , for treating an individual for acute myeloid leukemia.
14. The method of claim 2 for treating an individual for myelodysplastic syndrome.
15. The method of claim 1 , for treating an individual for acute myeloid leukemia.
16. The method of claim 1 , for treating an individual for myelodysplastic syndrome.
17. A kit comprising, in a first compartment, a compound according to Formula I:
wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound, and, in a second compartment, a DNA methyltransferase inhibitor selected from the group consisting of azacitidine, procaine, procainamide and epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
18. The kit of claim 17 , wherein the at least one DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof.
19. The kit of claim 17 , wherein the at least one DNA methyltransferase inhibitor is procaine or procainamide, or a pharmaceutically acceptable salt thereof.
20. The kit of claim 17 , wherein the at least one DNA methyltransferase inhibitor is epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
21. The kit of claim 17 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxy styryl sulfonyl)methyl)-2-methoxyphenylamino)acetic acid, or a pharmaceutically acceptable salt thereof.
22. The kit of claim 17 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt.
23. The kit of claim 17 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt and the DNA methyltransferase inhibitor is azacitidine.
24. A composition comprising at least one compound according to Formula I:
wherein R 1 is selected from the group consisting of —NH 2 , —NH—CH 2 —CO 2 H, —NH—CH(CH 3 )—CO 2 H, and —NH—C(CH 3 ) 2 —CO 2 H, or a pharmaceutically acceptable salt of such a compound, and at least one DNA methyltransferase inhibitor selected from the group consisting of azacitidine, procaine, procainamide and epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
25. The composition of claim 24 , wherein the at least one DNA methyltransferase inhibitor is azacitidine, or a pharmaceutically acceptable salt thereof.
26. The composition of claim 24 , wherein the at least one DNA methyltransferase inhibitor is procaine or procainamide, or a pharmaceutically acceptable salt thereof.
27. The composition of claim 24 , wherein the at least one DNA methyltransferase inhibitor is epigallocatechin gallate, or a pharmaceutically acceptable salt thereof.
28. The composition of claim 24 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid, or a pharmaceutically acceptable salt thereof.
29. The composition of claim 24 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt.
30. The composition of claim 24 , wherein the compound according to Formula I is (E)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid sodium salt and the DNA methyltransferase inhibitor is azacitidine.