Compositions and methods for inhibiting ACSS2
The present invention provides compositions and methods for inhibiting ACSS2 for modulating histone acetylation or for treating or preventing a neurological disease or disorder.
1. A method for treating a memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2), the method comprising administering a composition comprising an inhibitor of ACSS2 to a subject in need thereof;
wherein the inhibitor of ACSS2 is a small molecule;
wherein the small molecule is selected from the group consisting of a compound having the structure of:
wherein X 41 is selected from the group consisting of O and S;
R 41 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, unsubstituted aryl, heteroaryl, and combinations thereof, wherein R 41 may be optionally substituted; and
R 42 and R 43 are each independently selected from the group consisting of phenyl and thiophenyl; and
wherein the memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2) is an addiction to at least one selected from the group consisting of alcohol, tobacco, cocaine, and opioids.
2. The method of claim 1 , wherein the small molecule is selected from the group consisting of a compound having the structure
wherein, X 41 is selected from the group consisting of O and S;
R 41 is selected from the group consisting of alkyl, cycloalkyl, heterocyclyl, heteroaryl, and combinations thereof, wherein R 41 may be optionally substituted; and
R 42 and R 43 are each independently selected from the group consisting of phenyl and thiophenyl; and
3. The method of claim 1 , wherein the small molecule is selected from the group consisting of
4. A compound having the structure of:
wherein X 41 is selected from the group consisting of O and S;
R 41 is selected from the group consisting of adamantly, furanyl, heterocyclyl, and combinations thereof, wherein R 41 may be optionally substituted; and
R 42 and R 43 are each thiophenyl.
5. The compound of claim 4 , wherein the compound having the structure of Formula (4) is selected from the group consisting of
6. The method of claim 1 , wherein the memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2) is an addiction to alcohol.
7. The method of claim 1 , wherein the memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2) is an addiction to cocaine.
8. The method of claim 1 , wherein the memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2) is an addiction to tobacco.
9. The method of claim 1 , wherein the memory-related disease or disorder associated with acetyl-CoA synthetase 2 (ACSS2) is an addiction to opioids.
10. The compound of claim 4 , wherein the heterocyclyl is selected from the group consisting of morpholinyl, piperidnyl, pyrrolidinyl, and any combination thereof.
11. The compound of claim 4 , wherein R 41 is selected from the group consisting of adamantly, morpholinyl, piperidnyl, pyrrolidinyl, furanyl, and combinations thereof, wherein R 41 may be optionally substituted.