Ras inhibitors
The disclosure features macrocyclic compounds, and pharmaceutical compositions and protein complexes thereof, capable of inhibiting Ras proteins, and their uses in the treatment of cancers.
1. A compound, or a pharmaceutically acceptable salt thereof, selected from
2. A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, of claim 1 and a pharmaceutically acceptable excipient.
3. A method of treating cancer comprising a Ras mutation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, of claim 1 .
4. A method of treating a Ras protein-related disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, of claim 1 .
5. The method of claim 3 , wherein the cancer is pancreatic cancer, colorectal cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, ovarian cancer or uterine cancer.
6. The method of claim 3 , wherein the Ras mutation is at position 12, 13, or 61.
7. The method of claim 3 , wherein the Ras mutation is K-Ras G12C, K-Ras G12D, K-ras G12V, K-Ras G12S, K-Ras G13C, K-Ras G13D, or K-Ras Q61L.