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 formulas (I)-(XXVI) as disclosed herein to inhibit transcription factor Late SV40 Factor (LSF) for treatment of cancer, e.g., HCC.
1. A method of inhibiting LSF in a subject, the method comprising administering to the subject an effective amount of a compound of formula (III), wherein the formula (III) has the structure:
wherein:
R 1 is aryl, wherein the aryl can be optionally substituted with C 1 -C 6 alkoxyl at ortho-position;
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 of hydrogen and C 1 -C 6 alkyl;
R 6 and R 7 are hydrogen;
R 10 and R 11 are hydrogen;
or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
2. The method of claim 1 , wherein the compound of formula (I) is of formula (IV), wherein formula (IV) has the structure:
or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
3. The method of claim 1 , wherein the compound of formula (III) is selected from the group consisting of compounds of formulae (IV), (V), (VI), (VIII), (XII), (XIII) and (XXV):
or enantiomers, prodrugs, derivatives, and pharmaceutically acceptable salts thereof.
4. The method of claim 1 , wherein the subject suffers from or is at risk of cancer.
5. The method of claim 4 , wherein the cancer is hepatocellular carcinoma (HCC).
6. The method of claim 4 , wherein the cancer is selected from the group consisting of: breast cancer, colon 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.
7. The method of claim 1 , wherein the subject suffers from or is at risk of HIV or is in need of lower inflammatory responses.
8. The method of claim 1 , wherein R 1 is aryl optionally substituted with C 1 -C 4 alkoxy.
9. The method of claim 1 , wherein R 1 is aryl optionally substituted with ethoxy, propyloxy, isopropyloxy, or butyloxy.