Treatment of cancer

Abstract

The present invention provides compositions of matter, kits and methods for their use in the treatment of cancer. In particular, the invention provides compositions and methods for treating cancer in a subject by inhibiting a poly-ADP-ribose polymerase, as well as providing formulations and modes of administering such compositions.

1 - 3 . (canceled) 
     
     
         4 . A method of treating a cancer comprising administering to a subject in need thereof an effective amount of a composition comprising an isolated compound of formula (IIa): 
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2 , R 3 , R 4 , and R 5  substituent is always sulfur, and where R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of hydrogen, hydroxy, amino, nitro, iodo, bromo, fluoro, chloro, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 3 -C 7 ) cycloalkyl, and phenyl, wherein at least two of the five R 1 , R 2 , R 3 , R 4 , and R 5  substituents are always hydrogen, and wherein the sulfur-containing substituent is not a thiol, or a pharmaceutically acceptable salt thereof. 
     
     
         5 . A method of treating a cancer comprising administering to a subject in need thereof an effective amount of a composition comprising one or more isolated compound(s) selected from a group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof, and a compound of the formula MS213 
       
         
           
           
               
               
           
         
       
       wherein R 6  is selected from the group consisting of alkyl (C 1 -C 8 ), alkoxy (C 1 -C 8 ), isoquinolinones, indoles, thiazole, oxazole, oxadiazole, thiophene, and phenyl or a salt thereof. 
     
     
         6 . The method of  claim 4 , further comprising administering an effective amount of buthionine sulfoximine. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 4 , wherein a tumor cell undergoes apoptosis, cell cycle arrest, and/or necrosis in a patient. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 4 , wherein the compound is an isolated compound of the structural formula (IIa): 
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2 , R 3 , R 4 , and R 5  substituents is always a sulfur-containing substituent and where R 1 , R 2 , R 3 , R 4 , and R 5  are independently selected from the group consisting of hydrogen, hydroxy, amino, nitro, iodo, bromo, fluoro, (C 1 -C 6 ) alkyl, (C 1 -C 6 ) alkoxy, (C 3 -C 7 ) cycloalkyl, and phenyl, wherein at least two of the five R 1 , R 2 , R 3 , R 4 , and R 5  substituents are always hydrogen, and wherein the sulfur-containing substituent is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 4 , wherein the compound is an isolated compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof, and a compound of the formula MS213 
       
         
           
           
               
               
           
         
       
       wherein R 6  is selected from the group consisting of alkoxy (C 1 -C 8 ), isoquinolinones, thiazole, oxazole, oxadiazole, and thiophene, or a salt thereof. 
     
     
         13 . The method of  claim 12 , wherein said compound is in the form of a pharmaceutically acceptable salt thereof. 
     
     
         14 . The method of  claim 4 , wherein the compound is an isolated compound of the formula MS213: 
       
         
           
           
               
               
           
         
       
       wherein R 6  is selected from the group consisting of alkoxy (C 1 -C 8 ), isoquinolinones, thiazole, oxazole, oxadiazole, and thiophene, or a salt thereof.