Compounds and uses thereof

Abstract

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.

What is claimed is: 
     
         1 . A method of treating metastatic uveal melanoma in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having the formula (A): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the compound of formula (A) has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . The method of  claim 2 , wherein the compound of formula (A) has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         4 . The method of  claim 1 , wherein the compound of formula (A) has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         5 . The method of  claim 1 , wherein the method comprises administering a pharmaceutical composition comprising the compound of formula (A) having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein each substituent D is a position that is deuterium enriched within the pharmaceutical composition. 
       
     
     
         6 . The method of  claim 5 , wherein the pharmaceutical composition comprises the compound of formula (A) having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein each substituent D is a position that is deuterium enriched within the pharmaceutical composition. 
       
     
     
         7 . The method of  claim 6 , wherein the pharmaceutical composition comprises the compound of formula (A) having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein each substituent D is a position that is deuterium enriched within the pharmaceutical composition. 
       
     
     
         8 . The method of  claim 5 , wherein the pharmaceutical composition comprises the compound of formula (A) having the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, 
         wherein each substituent D is a position that is deuterium enriched within the pharmaceutical composition. 
       
     
     
         9 . The method of  claim 1 , wherein the metastatic uveal melanoma expresses BRG1 and/or BRM protein. 
     
     
         10 . The method of  claim 1 , wherein the subject or metastatic uveal melanoma has an BRG1 loss of function mutation. 
     
     
         11 . The method of  claim 10 , wherein the BRG1 loss of function mutation is in the ATPase catalytic domain of the protein. 
     
     
         12 . The method of  claim 10 , wherein the BRG1 loss of function mutation is a deletion at the C-terminus of BRG1. 
     
     
         13 . The method of  claim 1 , wherein the metastatic uveal melanoma does not have, or has been determined not to have, an epidermal growth factor receptor mutation and/or an anaplastic lymphoma kinase driver mutation. 
     
     
         14 . The method  claim 1 , wherein the metastatic uveal melanoma has, or has been determined to have, a KRAS mutation, a mutation in GNAQ, a mutation in GNA11, a mutation in PLCB4, a mutation in CYSLTR2, a mutation in BAP1, a mutation in SF3B1, a mutation in EIF1AX, a TFE3 translocation, a TFEB translocation, a MITF translocation, an EZH2 mutation, a SUZ12 mutation, and/or an EED mutation. 
     
     
         15 . The method of  claim 1 , wherein effective amount decreases the activity of a BAF complex in the subject. 
     
     
         16 . The method of  claim 1 , wherein the effective amount inhibits BRM and/or BRG1 in the subject. 
     
     
         17 . The method of  claim 1 , wherein the effective amount induces apoptosis in the subject. 
     
     
         18 . The method of  claim 1 , wherein the metastatic uveal melanoma is resistant to, or failed to respond to, prior treatment with an anticancer therapy. 
     
     
         19 . The method of  claim 1 , wherein the method further comprises administering to the subject an anticancer therapy. 
     
     
         20 . The method of  claim 19 , wherein the anticancer therapy is surgery, a MEK inhibitor, and/or a PKC inhibitor, or a combination thereof.