Fatty acid synthase inhibitors
The present disclosure relates to a method for inhibiting Fatty Acid Synthase (FASN) with a FASN inhibitor, methods for treating cancer and viral infections with a FASN inhibitor, and compounds and compositions inhibiting FASN.
1. A method of promoting apoptosis in a cancer cell dependent on FASN activity, the method comprising contacting the cell with an inhibitor that binds to the FASN purine-binding cofactor domain.
2. The method of claim 1 , wherein the inhibitor does not bind to the substrate domain.
3. The method of claim 1 , wherein the inhibitor possesses a thiophenopyrimidine scaffold.
4. The method of claim 1 , wherein the inhibitor possesses a thieno[2,3-d]pyrimidine scaffold.
5. The method of claim 1 , wherein the inhibitor is N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof.
6. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject, a therapeutically effective amount of a FASN inhibitor that binds to the FASN purine-binding cofactor domain.
7. The method of claim 6 , wherein the inhibitor does not bind to the substrate domain.
8. The method of claim 6 , wherein the cancer is selected from the group consisting of HER2-positive breast cancer, triple negative breast cancer, melanoma, hepatocellular carcinoma, and leukemia.
9. The method of claim 6 , wherein the inhibitor possesses a thiophenopyrimidine scaffold.
10. The method of claim 6 , wherein the inhibitor possesses a thieno[2,3-d]pyrimidine scaffold.
11. The method of claim 6 , wherein the inhibitor is N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof.
12. The method of claim 6 , wherein the inhibitor is co-administered with a platinum-based antineoplastic compound.
13. The method of claim 12 , wherein the inhibitor is co-administered with carboplatin or cisplatin.
14. The method of claim 12 , wherein the inhibitor is co-administered with carboplatin.
15. The method of claim 12 , wherein the platinum-based antineoplastic compound is administered at a dosage less than that required when administered in the absence of a FASN inhibitor.
16. A pharmaceutical composition comprising N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
17. The method of claim 1 , wherein the inhibitor is (R)—N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine or a pharmaceutically acceptable salt thereof.
18. The method of claim 1 , wherein the inhibitor is (S)—N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine or a pharmaceutically acceptable salt thereof.
19. The method of claim 6 , wherein the inhibitor is (R)—N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine or a pharmaceutically acceptable salt thereof.
20. The method of claim 6 , wherein the inhibitor is (S)—N-(1-benzylpyrrolidin-3-yl)-5,6-dimethylthieno[2,3-d]pyrimidin-4-amine or a pharmaceutically acceptable salt thereof.