PRMT5 inhibitors and uses thereof
View Patent ↗Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.
1. A method of inhibiting PRMT5 comprising contacting a cell with an effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof.
2. A method of altering gene expression comprising contacting a cell with an effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof.
3. A method of altering transcription comprising contacting a cell with an effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof.
4. The method of claim 1 , wherein the cell is in vitro.
5. The method of claim 1 , wherein the cell is in a subject.
6. A method of treating cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the cancer is breast cancer, esophageal cancer, bladder cancer, lymphoma, medulloblastoma, rectum adenocarcinoma, colon adenocarcinoma, gastric cancer, liver cancer, adenoid cystic carcinoma, lung adenocarcinoma, head and neck squamous cell carcinoma, brain cancer, hepatocellular carcinoma, renal cell carcinoma, oligodendroglioma, ovarian clear cell carcinoma, ovarian serous cystadenocarcinoma, hematopoietic cancer, lung cancer, prostate cancer, melanoma, or pancreatic cancer.
8. A method of treating a metabolic disorder or a blood disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula:
or a pharmaceutically acceptable salt thereof,
wherein the metabolic disorder is diabetes or obesity, and
wherein the blood disorder is a hemoglobinopathy.
9. The method of claim 8 , comprising treating a metabolic disorder, wherein the metabolic disorder is diabetes.
10. The method of claim 8 , comprising treating a metabolic disorder, wherein the metabolic disorder is obesity.
11. The method of claim 8 , comprising treating a hemoglobinopathy, wherein the hemoglobinopathy is sickle cell anemia.
12. The method of claim 8 , comprising treating a hemoglobinopathy, wherein the hemoglobinopathy is β-thalessemia.
13. The method of claim 2 , wherein the cell is in vitro.
14. The method of claim 2 , wherein the cell is in a subject.
15. The method of claim 3 , wherein the cell is in vitro.
16. The method of claim 3 , wherein the cell is in a subject.
17. The method of claim 6 , wherein the compound is:
18. The method of claim 6 , wherein the compound is a pharmaceutically acceptable salt of:
19. The method of claim 8 , comprising treating a hemoglobinopathy.
20. The method of claim 7 , wherein the cancer is breast cancer.
21. The method of claim 7 , wherein the cancer is bladder cancer.
22. The method of claim 7 , wherein the cancer is lymphoma.
23. The method of claim 7 , wherein the cancer is brain cancer.