STAT3 inhibitors and uses thereof
Described herein, inter alia, are STAT-binding nucleic acids-including compositions and methods of using the same.
1. A method of treating lymphoma, leukemia, or prostate cancer in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound which comprises SEQ ID NO:23 covalently bonded to SEQ ID NO:12.
2. The method of claim 1 for treating leukemia.
3. The method of claim 2 , wherein the leukemia is acute myeloid leukemia.
4. The method of claim 1 , for treating lymphoma.
5. The method of claim 4 , wherein the lymphoma is non-Hodgkin's lymphoma.
6. The method of claim 5 , wherein the non-Hodgkin's lymphoma is a large cell lymphoma.
7. The method of claim 5 , wherein the non-Hodgkin's lymphoma is Burkitt lymphoma or small cell lymphoma.
8. The method of claim 4 , wherein the lymphoma is B cell lymphoma.
9. The method of claim 1 , comprising systemically administering the compound to the patient.
10. The method of claim 1 , comprising intravenously administering the compound to the patient.
11. The method of claim 1 , comprising intratumorally administering the compound to the patient.
12. A method of treating lymphoma, leukemia, or prostate cancer in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound which comprises a toll-like receptor (TLR)-binding nucleic acid substituent conjugated to a signal transducer and activator of transcription (STAT)-binding nucleic acid substituent, wherein the STAT-binding nucleic acid substituent is capable of binding to a STAT transcription factor.
13. The method of claim 12 for treating leukemia.
14. The method of claim 13 , wherein the leukemia is acute myeloid leukemia.
15. The method of claim 12 , for treating lymphoma.
16. The method of claim 15 , wherein the lymphoma is non-Hodgkin's lymphoma.
17. The method of claim 16 , wherein-the TLR9-binding DNA substituent comprises a Class A CpG DNA sequence, a Class B CpG DNA sequence, or a Class C CpG DNA sequence.
18. The method of claim 12 , wherein the toll-like receptor (TLR)-binding nucleic acid substituent is a toll-like receptor 9 (TLR9)-binding DNA substituent; and wherein the activator of transcription (STAT)-binding nucleic acid substituent is a signal transducer and activator of transcription 3 (STAT3)-binding DNA substituent.
19. The method of claim 12 , wherein the TLR-binding nucleic acid substituent is a nucleic acid sequence comprising SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, or SEQ ID NO:24.
20. The method of claim 12 , wherein the STAT3-binding DNA substituent comprises a first STAT3-binding DNA sequence covalently bound to a second STAT3-binding DNA sequence by a spacer; and the spacer is a substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, or substituted or unsubstituted heteroarylene.