Proteasome regulation of NF-kB activity

Abstract

Disclosed herein is a method for regulating the activity of NF-κB in an animal comprising contacting cells of the animal with certain proteasome inhibitors.

What is claimed is:  
     
         1 . A method for reducing the cellular content and activity of NF-κB in an animal comprising contacting cells of the animal with inhibitors of proteasome function or ubiquitin conjugation.  
     
     
         2 . A method for reducing the cellular content and activity of NF-κB in an animal comprising contacting cells of the animal with a proteasome function or ubiquitin conjugation inhibitor of the structure:  
       
         
           
           
               
               
           
         
       
       where 
 P is an amino-group-protecting moiety;  
 B 1 , B 2 , B 3 , and B 4  are independently selected from the group consisting of  
                     
  X 1 , X 2 , and X 3  are independently selected from group consisting of  
                     
 R is a hydrogen, alkyl, acyl, or carboxyl;  
 R 1 , R 2 , R 3 , and R 4  are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, and —CH 2 —R 5 ,  
 where R 5  is aryl, aralkyl, alkaryl, cycloalkyl or —Y—R 6 , 
 where Y is a chalcogen, and R 6  is alkyl; and  
 A is 0 or 1.  
 
 
     
     
         3 . The method of  claim 2  wherein P is  
       
         
           
           
               
               
           
         
       
       and R 1  is alkyl, aryl, alkaryl, aralkyl, alkoxy, aryloxy, alkaryloxy, or aralkoxy.  
     
     
         4 . The method of  claim 3  wherein X 1 , X 2 , and X 3  are  
       
         
           
           
               
               
           
         
       
     
     
         5 . The method of  claim 4  wherein A is 0 and B 1 , B 2 , and B 3  are  
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 5  wherein R 1  and R 2  are independently selected from the group consisting of alkyl and —CH 2 —R 5 , where R 5  is cyclohexyl or naphthyl.  
     
     
         7 . The method of  claim 6  wherein R1 and R 2  are isobutyl.  
     
     
         8 . The method of  claim 2  wherein the proteasome inhibitor is selected from the group consisting of  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         9 . The method of  claim 2  wherein the proteasome inhibitor is selected from the group consisting of