Ras inhibitors

Abstract

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 - 32 . (canceled) 
     
     
         33 . A compound, or a pharmaceutically acceptable salt thereof, selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         34 . A pharmaceutical composition comprising a compound, or a pharmaceutically acceptable salt thereof, of  claim 33  or  claim 48  and a pharmaceutically acceptable excipient. 
     
     
         35 . A method of treating cancer 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 33  or  claim 48 . 
     
     
         36 - 39 . (canceled) 
     
     
         40 . 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 33  or  claim 48 . 
     
     
         41 - 43 . (canceled) 
     
     
         44 . The method of  claim 35 , wherein the cancer is pancreatic cancer, colorectal cancer, non-small cell lung cancer, gastric cancer, esophageal cancer, ovarian cancer, or uterine cancer. 
     
     
         45 . The method of  claim 44 , wherein the cancer comprises a Ras mutation. 
     
     
         46 . The method of  claim 45 , wherein the Ras mutation is at position 12, 13, or 61. 
     
     
         47 . The method of  claim 45 , 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, or a combination thereof. 
     
     
         48 . A compound, or a stereoisomer thereof, or a pharmaceutically acceptable salt of such a stereoisomer, selected from: