Inhibitors of late SV40 factor (LSF) as cancer chemotherapeutics
The present invention is directed to methods, compositions and kits for treatment of cancer, e.g. heptacellular carcinoma. In some embodiments, the present invention discloses the use of a small-molecule compound of formula (I)-(XXVI) and (III′) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC.
1. A compound of formula (III′), wherein the Formula (III′) has the structure:
wherein:
R 1′ is an aryl substituted with at least one C 1 -C 6 alkoxyl and at least one di(C 1 -C 24 alkyl)amino, wherein the substituted aryl can be optionally further substituted with halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 heteroalkyl, di(C 1 -C 24 alkyl)amino or combinations thereof;
R 2 and R 3 are hydrogen or R 2 and R 3 together form a second bond between the carbons to which they are attached;
R 4 is hydrogen;
R 5 is selected from the group consisting of hydrogen and C 1 -C 6 alkyl;
R 6 and R 7 are each independently selected from the group consisting of hydrogen, F, Br, Cl and I;
R 10 and R 11 are each independently selected from the group consisting of hydrogen, F, Br, Cl, and I;
or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof, and wherein the compound is capable of inhibiting late SV40 factor (LSF).
2. The compound of claim 1 , wherein R 1′ is a phenyl substituted with at least one C 1 -C 6 alkoxyl and at least one di(C 1 -C 24 alkyl)amino.
3. The compound of 2, wherein R 1′ is
wherein R 21 is C 1 -C 6 alkyl and R 22 and R 23 are independently selected C 1 -C 24 alkyl.
4. The compound of claim 3 , wherein R 22 and R 23 are independently selected C 1 -C 6 alkyl.
5. The compound of claim 3 , wherein R 1′ is
6. A method of inhibiting LSF in a subject, the method comprising administering an effective amount of a compound of claim 1 to a subject in need thereof.
7. The compound of claim 1 , wherein the compound is FQI-34 having a structure:
8. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient or carrier.
9. The compound of claim 6 , wherein R 1′ is
10. The method of claim 9 , wherein the subject suffers from or is at risk of cancer.
11. The method of claim 10 , wherein the cancer is hepatocellular carcinoma (HCC).
12. The method of claim 10 , wherein the cancer is selected from the group consisting of breast cancer, color cancer, ovarian cancer, lung cancer, kidney cancer, cancers of the hematopoietic system, cancers of the endometrium, cervical cancer, cancers of the upper digestive tract, stomach cancer, liver cancers and cancers of the small intestine.
13. The method of claim 6 , wherein the subject suffers from or is at risk of HIV or is in need of lower inflammatory responses.
14. The method of claim 6 , wherein the compound is FQI-34 having a structure: