Modulation of signal transducer and activator of transcription 3 (STAT3)expression
View Patent ↗Disclosed herein are antisense compounds and methods for decreasing STAT3 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate hyperproliferative diseases.
1. A compound comprising a single-stranded modified oligonucleotide consisting of 16 linked nucleosides having a nucleobase sequence consisting of the sequence of SEQ ID NO: 245, or a pharmaceutically acceptable salt thereof, wherein the modified oligonucleotide comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of 3 linked nucleosides; and
a 3′ wing segment consisting of 3 linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment;
wherein each nucleoside of each wing segment comprises a constrained ethyl nucleoside;
wherein each internucleoside linkage of the modified oligonucleotide is a phosphorothioate linkage; and wherein each cytosine of the modified oligonucleotide is a 5 ′-methylcytosine.
2. A method of treating cancer in an animal, comprising administering to the animal the compound of claim 1 , or a pharmaceutical salt thereof, thereby treating the cancer.
3. The method of claim 2 , wherein administering the compound, or a pharmaceutical salt thereof, reduces tumor size in the animal.
4. The method of claim 2 , wherein administering the compound, or a pharmaceutical salt thereof, reduces tumor volume in the animal.
5. The method of claim 2 , wherein administering the compound, or a pharmaceutical salt thereof, prolongs survival of the animal.
6. A method of reducing expression of STAT3 in an animal, comprising administering to the animal the compound of claim 1 , or a pharmaceutical salt thereof.
7. A composition comprising the compound of claim 1 , or a pharmaceutical salt thereof, and a pharmaceutically acceptable diluent or carrier.
8. A method of treating cancer in an animal, comprising administering to the animal the composition of claim 7 , thereby treating the cancer.
9. The method of claim 8 , wherein administering the composition reduces tumor size in the animal.
10. The method of claim 8 , wherein administering the composition reduces tumor volume in the animal.
11. The method of claim 8 , wherein administering the composition prolongs survival of the animal.
12. The method of claim 8 , wherein the animal is a human.
13. The method of claim 2 , wherein the animal is a human.
14. The compound of claim 1 , or a pharmaceutical salt thereof, wherein the oligonucleotide is covalently linked to a conjugate.
15. The compound of claim 14 , or a pharmaceutical salt thereof, wherein the conjugate comprises a carbohydrate group.
16. A composition comprising the compound of claim 14 , or a pharmaceutical salt thereof, and a pharmaceutically acceptable diluent or carrier.
17. A composition comprising the compound of claim 15 , or a pharmaceutical salt thereof, and a pharmaceutically acceptable diluent or carrier.