Compositions and methods for treating cancers
AssigneeCedars-Sinai Medical Center
InventorsMouad Edderkaoui, Ramachandran Murali, Stephen Pandol
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Abstract
The invention describes compounds that inhibit both HDAC and GSK3β (i.e., HDAC/GSK3β dual inhibitors). The invention further describes compositions containing these HDAC/GSK3β dual inhibitors, as well as methods and kits using these HDAC/GSK3β dual inhibitors to treat various medical conditions. The invention also provides methods and kits using a HDAC inhibitor and a GSK3β to treat various medical conditions, and compositions containing a HDAC inhibitor and a GSK3β. Medical conditions treatable with various embodiments of the invention include but are not limited to cancers and tumors.
Claims107
A compound of Formula (IV):
- wherein:
- L1 and L2 are independently a linker;
- R1 is an aromatic moiety, alkyl, acyl, cyclyl or heterocyclyl, each of which can be optionally substituted;
- R2 is hydrogen, lower alkyl, cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
- R3 is absent or an aromatic moiety, which can be optionally substituted;
- p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
- and
- wherein -L1R1 is linked to one nitorgen of the thiadiazolidine ring and —(CH2)p—R3-L2-C(O)NHOR2 is linked to the other nitorgen of the thiadiazolidine ring.
A compound of Formula (V):
- wherein:
- L1 and L2 are independently a linker;
- R1 is an aromatic moiety, alkyl, acyl, cyclyl or heterocyclyl, each of which can be optionally substituted;
- R2 is hydrogen, lower alkyl, cyclyl, heterocyclyl, aryl, or heteroaryl, each of which can be optionally substituted;
- R3 is absent or an aromatic moiety, which can be optionally substituted;
- and
- p is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10.
A composition comprising a dual inhibitor of HDAC and GSK3β.
A method of treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, comprising:
- administering a therapeutically effective amount of a dual inhibitor of HDAC and GSK3β to the subject, thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject.
The method of claim 2727, further comprising administering an additional anti-cancer therapy.
A kit for treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, comprising:
- a dual inhibitor of HDAC and GSK3β;
- and
- instructions for using the dual inhibitor to treat, prevent, reduce the likelihood of having, reduce the severity of and/or slow the progression of the condition in the subject.
A composition comprising a HDAC inhibitor and a GSK3β inhibitor.
A method of treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, comprising:
- administering a therapeutically effective amount of a HDAC inhibitor and a GSK3β inhibitor to the subject, thereby treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of the condition in the subject.
The method of claim 6627, further comprising administering an additional anti-cancer therapy.
A kit for treating, preventing, reducing the likelihood of having, reducing the severity of and/or slowing the progression of a condition in a subject, comprising:
- a HDAC inhibitor;
- a GSK3β inhibitor;
- and
- instructions for using the HDAC inhibitor and the GSK3β inhibitor to treat, prevent, reduce the likelihood of having, reduce the severity of and/or slow the progression of the condition in the subject.
Dependencies are inferred from the claim text.