Use of cyclic depsipeptides to inhibit kallikrein 7

Abstract

The present application relate to cyclic depsipeptides, or derivatives thereof, having the formula (I), and uses thereof, e.g. as inhibitors of kallikrein 7.

1 . Method of treating a subject suffering from a kallikrein 7-dependent disease, comprising: administering to said subject a therapeutically effective amount of a cyclic depsipeptide, or a derivative thereof, having the structure of formula (I): 
       
         
           
           
               
               
           
         
         wherein the ester bond is found between the carboxy group of A7 and the hydroxy group of A2, 
         wherein X and A 1  are each independently optional, 
         and wherein
 X is any chemical residue 
 A 1  is a standard amino acid, 
 A 2  is threonine or serine or 5-methylhydroxyproline, 
 A 3  is a non-basic standard amino acid or a non-basic non-standard amino acid, or a non-basic derivative thereof, 
 A 4  is Ahp, dehydro-AHP, proline or a derivative thereof, 
 A 5  is isoleucine, leucine, phenylalanin, prolin, threonine, or valine, 
 A 6  is alanine, phenylalanine, tryptophan, tyrosine or a derivative thereof 
 A 7  is leucine, isoleucine or valine, 
 
         wherein the nitrogen atom of the amid bond between A5 and A6 can be substituted with a methyl 
         or a pharmaceutically acceptable salt of cyclic depsipeptide or a derivative thereof. 
       
     
     
         2 . The method of  claim 1  wherein the kallikrein 7-dependent disease is cancer. 
     
     
         3 . The method of  claim 1  wherein X is H or an acyl residue. 
     
     
         4 . The method of  claim 1  wherein X is CH 3 CH 2 CH(CH 3 )CO, (CH 3 ) 2 CHCH 2 CO or (CH 3 ) 2 CHCO. 
     
     
         5 - 7 . (canceled) 
     
     
         8 . The method of  claim 2  wherein X is H or an acyl residue. 
     
     
         9 . The method of  claim 2  wherein X is CH 3 CH 2 CH(CH 3 )CO, (CH 3 ) 2 CHCH 2 CO or (CH 3 ) 2 CHCO. 
     
     
         10 . The method according to  claim 2  wherein cancer is ovarian cancer. 
     
     
         11 . The method according to  claim 8  wherein cancer is ovarian cancer. 
     
     
         12 . The method according to  claim 9  wherein cancer is ovarian cancer.