Inhibition of leukemic stem cells by PP2A activating agents
A method of inhibiting the growth of leukemic hematopoietic stem cells in a subject with leukemia is described. The method includes administering a therapeutically effective amount of a composition including a compound of formula I: I wherein R 1 is independently selected from hydrogen and methyl; R 2 is selected from the group consisting of 4,8-dimethyl-non-1-enyl, 4,8-dimethyl-nonyl, non-1-enyl, and nonanyl groups; X is a carboxyl, phosphonic, or sulfonic moiety, and n is an integer from 1 to 6, or a compound of Formula II: II wherein R 1 is a C 6 -C 12 alkyl or C 6 -C 12 alkoxy group; R 2 is independently selected from the group consisting of hydrogen, methoxy, and hydroxyl; and R 3 is an alkyl or cycloalkyl group; or a pharmaceutically acceptable salt thereof.
1. A method of inhibiting the growth of leukemic hematopoietic stem cells in a subject with leukemia, comprising administering a therapeutically effective amount of a composition including a compound of Formula II:
wherein R 1 is a C 6 -C 12 alkyl or C 6 -C 12 alkoxy group;
R 2 is independently selected from the group consisting of hydrogen, methoxy, and hydroxyl; and
R 3 is a an alkyl or cycloalkyl group; or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the leukemia is a Ph+ leukemia.
3. The method of claim 2 , wherein the Ph+ leukemia is chronic myelogenous leukemia.
4. The method of claim 1 , wherein the composition has a cytotoxic effect on leukemic hematopoietic stem cells.
5. The method of claim 1 , wherein R 1 is C 6 -C 12 alkyl.
6. The method of claim 1 , wherein R 1 is C 6 -C 12 alkoxy.
7. The method of claim 1 , wherein R 2 is hydrogen and R 3 is selected from the group consisting of propyl, isopropyl, isobutyl, cyclopropyl methyl, and cyclobutyl methyl.
8. The method of claim 1 , wherein R 1 is C 8 alkyl or C 8 alkoxy.
9. The method of claim 8 , wherein R 2 is hydrogen and R 3 is selected from the group consisting of propyl, isopropyl, isobutyl, cyclopropyl methyl, and cyclobutyl methyl.
10. The method of claim 8 , wherein the compound has the structure
11. The method of claim 8 , wherein the compound has the structure