Stat3 inhibiting compositions and methods

Abstract

STAT 3 inhibiting molecules and composition prevent intraoccular neovascularization and inflammation. STA-21-related compounds, for example CLT-005, are shown to prevent dimerization of STAT 3 , thereby inhibiting STAT 3 activity. Inhibition of activity is shown to reduce intraoccular inflammation and neovascularization, symptoms of eye-related diseases such as age-related macular degeneration. Inhibition of STAT 3 prevents STAT 3 from transcriptionally activating downstream gene targets that are known to be associated with retinal inflammation and neovascularization and such disorders as age-related macular degeneration.

1 . A composition comprising:
 an effective amount of an agent having the formula:   
     
       
         
         
             
             
         
       
       and a pharmaceutically acceptable carrier. 
     
   
   
       2 . The composition of  claim 1 , wherein the composition is prepared for administration to a subject having an eye-related disease. 
   
   
       3 . The composition of  claim 2 , wherein the eye-related disease is age-related macular degeneration. 
   
   
       4 . The composition of  claim 2 , wherein the eye-related disease is endophthalmitis. 
   
   
       5 . The method of  claim 1 , wherein the composition is prepared for administration to a subject to interfere with the dimerization of STAT 3  molecules. 
   
   
       6 . A composition comprising:
 a pharmaceutical carrier and a therapeutically effective amount an agent of the formula:   
     
       
         
         
             
             
         
       
       where R 1  and R 2  are independently selected from H, OH, and OMe. 
     
   
   
       7 . The composition of  claim 6 , wherein the agent is at least one of: 
     
       
         
         
             
             
         
       
     
   
   
       8 . The composition of  claim 6 , wherein the agent is: 
     
       
         
         
             
             
         
       
     
   
   
       9 . The composition of  claim 6 , wherein the composition is prepared for administration to a subject having an eye-related disease. 
   
   
       10 . The composition of  claim 9 , wherein the eye-related disease is age-related macular degeneration. 
   
   
       11 . The composition of  claim 9 , wherein the eye-related disease is endopthalmitis. 
   
   
       12 . The composition of  claim 6 , wherein the composition is prepared for administration to a subject to interfere with the dimerization of STAT 3  molecules. 
   
   
       13 . A method comprising:
 administering effective amount of STA-21 or a STA-21-related agent having the formula:   
     
       
         
         
             
             
         
       
       where R 1  and R 2  are independently selected from H, OH, and OMe; 
       to a subject having an eye-related disease. 
     
   
   
       14 . The method of  claim 13 , wherein the agent is: 
     
       
         
         
             
             
         
       
     
   
   
       15 . The method of  claim 13 , wherein the agent is at least one of: 
     
       
         
         
             
             
         
       
     
   
   
       16 . The composition of  claim 13 , wherein the eye-related disease is age-related macular degeneration. 
   
   
       17 . The composition of  claim 13 , wherein the eye-related disease is endopthalmitis. 
   
   
       18 . A method comprising:
 administering effective amount of a STA-21-related agent having the formula:   
     
       
         
         
             
             
         
       
     
     where R 1  and R 2  are independently selected from H, OH, and OMe;
 to a subject to disrupt dimerization of STAT 3 . 
 
   
   
       19 . The method of  claim 18 , wherein the subject has an eye-related disease. 
   
   
       20 . The method of  claim 19 , wherein the eye-related disease is selected from the group consisting of age-related macular degeneration and endopthalmitis.