HDAC8 inhibitors for treating cancer
Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.
1. A compound having the formula (I):
wherein:
R 1 is substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C 3 -C 7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl; and
R 2 is substituted or unsubstituted C 1 -C 20 alkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C 3 -C 7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl.
2. The compound of claim 1 , wherein R 1 is substituted or unsubstituted C 1 -C 4 alkoxy and R 2 is a substituted or unsubstituted C 4 -C 6 aryl.
3. The compound of claim 2 , wherein R 1 is unsubstituted C 1 -C 2 alkoxy and R 2 is unsubstituted C6 aryl.
4. The compound of claim 1 , wherein the compound has formula (II):
5. A compound selected from the group consisting of:
6. A method of inhibiting HDAC8 mediated deacetylation of p53, the method comprising contacting HDAC8 with the compound of claim 1 in the presence of p53, thereby inhibiting HDAC8 deacetylation of p53.
7. A method of activating p53 in vivo, the method comprising contacting a cell with the compound of claim 1 in the presence of HDAC8; wherein the cell is an AML cell.
8. The method of claim 7 , wherein the AML cell is an AML stem cell.
9. The compound of claim 1 , wherein:
R 1 is substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C 6 -C 7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl; and
R 2 is substituted or unsubstituted C 1 -C 20 alkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C 3 -C 7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C 6 -C 7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl.