Compounds for treatment of fibrosis diseases

Abstract

The present invention relates to compounds as inhibitor of WNT signal transduction pathway, as well as a composition comprising the same. Further, the present invention relates to the use of the compounds in the treatment of fibrosis.

1 . A method for reducing a symptom associated with cardiac hypertrophy related disease in a subject that is in need of such treatment, comprising:
 administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of a WNT signaling inhibitor, wherein said WNT signaling inhibitor inhibits porcupine (PORCN).   
     
     
         2 . The method of  claim 1 , wherein said WNT signaling inhibitor is a small organic molecule that inhibits WNT signaling activity and has a molecular weight not greater than about 800 g/mol. 
     
     
         3 . The method of  claim 1 , wherein said WNT signaling inhibitor is a compound having substituent groups that comprise at least one of H,  2 H,  3 H,  11 C,  13 C,  14 C,  15 N,  17 O,  18 O,  35 S,  18 F,  36 Cl, or  123 I. 
     
     
         4 . The method of  claim 1 , wherein said pharmaceutical composition is an injectable composition and is an aqueous isotonic solution or a suspension. 
     
     
         5 . The method of  claim 1 , wherein said pharmaceutical composition is a suppository and is prepared from fatty emulsions or suspensions. 
     
     
         6 . The method of  claim 1 , wherein said pharmaceutical composition further comprises adjuvants, wherein the adjuvants are preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure, or buffers, or a combination thereof. 
     
     
         7 . The method of  claim 6 , wherein said pharmaceutical composition is for topical application and is an aqueous solution, an ointment, a cream, or a gel. 
     
     
         8 . The method of  claim 1 , wherein the therapeutically effective amount of the compound is about 0.03 to 2.5 mg/kg of body weight at daily dosages. 
     
     
         9 . The method of  claim 8 , wherein the therapeutically effective amount of the compound is about 0.5 mg to about 500 mg for human. 
     
     
         10 . The method of  claim 1 , wherein said cardiac hypertrophy is load-induced cardiac hypertrophy. 
     
     
         11 . The method of  claim 1 , wherein said symptoms are reduced over a 28-day period. 
     
     
         12 . The method of  claim 11 , wherein said pharmaceutical composition is administered once daily for the 28-day period. 
     
     
         13 . The method of  claim 1 , wherein said symptoms are reduced over a 15-day period. 
     
     
         14 . The method of  claim 13 , wherein said pharmaceutical composition is administered once daily for the 15-day period. 
     
     
         15 . The method of  claim 1 , wherein said WNT signaling inhibitor has a core structure selected from the following core structures: 
       
         
           
           
               
               
           
         
       
     
     
         16 . The method of  claim 15 , wherein said core structure is one of the following core structures: 
       
         
           
           
               
               
           
         
       
     
     
         17 . The method of  claim 15 , wherein said core structure is one of the following core structures: