KRAS G12C inhibitors and methods of using the same
Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.
1. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
2. A compound, wherein the compound is:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
3. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the atropisomer thereof.
4. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a pharmaceutically acceptable salt of the atropisomer thereof.
5. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
6. A compound, wherein the compound is:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
7. A compound, wherein the compound is:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
8. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
9. A compound having a structure selected from:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
10. A compound, wherein the compound is:
or a stereoisomer thereof, an atropisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, or a pharmaceutically acceptable salt of the atropisomer thereof.
11. A pharmaceutical formulation comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
12. A method of inhibiting KRAS G12C in a cell, comprising contacting the cell with the compound of claim 1 .
13. A method of treating cancer in a subject comprising administering to the subject a therapeutically effective amount of the compound of claim 1 .
14. The method of claim 13 , wherein the cancer is lung cancer, pancreatic cancer, or colorectal cancer.
15. The method of claim 13 , further comprising administering to the patient in need thereof a therapeutically effective amount of an additional pharmaceutically active compound.
16. The method of claim 15 , wherein the additional pharmaceutically active compound is an anti-PD-1 antagonist.
17. The method of claim 15 , wherein the additional pharmaceutically active compound is nivolumab.
18. The method of claim 15 , wherein the additional pharmaceutically active compound is pembrolizumab.
19. The method of claim 15 , wherein the additional pharmaceutically active compound is AMG 404.