Cdc42 Inhibitor and Uses Thereof

Abstract

Compounds which inhibit the small G protein Rho GTPase cell division cycle protein Cdc42 are provided. Morphological analyses of filopodia, western blots of Ccd42 phosphorylation, and effects on cellular wound healing and on growth cone formation all demonstrate that the described compounds are able to inhibit all tested Cdc42-mediated processes. The compounds effectively inhibit, the effects of Cdc42 and effectively inhibit Cdc42-related cellular functions involving actin, such as Golgi organization and cell movement. Furthermore, the described Cdc42 inhibitor compounds may be provided as a medicament for the treatment of various conditions.

What is claimed is: 
     
         1 . A compound of structure A: 
       
         
           
           
               
               
           
         
         structure B: 
       
       
         
           
           
               
               
           
         
         or a combination thereof, wherein
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8  are each independently selected from the group consisting of fluoro, chloro, bromo, nitro, cyano, amino, methyl, hydroxylmethyl, trifluoromethyl, methoxy, trifluoromethyoxy, and ethyl; and 
 A, D, E, G, J, M, W, X, Y, Z are each selected from the group consisting of nitrogen, carbon, and substituted carbon, and any of A, D, E, G, J, M, W, X, Y, Z may be missing, such that the ring structure is less than a six-membered ring. 
 
       
     
     
         2 . A compound of structure C: 
       
         
           
           
               
               
           
         
         where R 1  and R 2  are independently selected from the group consisting of alkyl, cyclic alkyl, aryl, and substituted aryl. 
       
     
     
         3 . The compound of  claim 2  wherein R 1  is selected from the group consisting of 
       
         
           
           
               
               
           
         
         and R2 is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
     
     
         4 . The compound of  claim 2  wherein the compound is according to formula I: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 1  wherein the compound is prepared as a medicament for at least one of treatment of malignant tumors, prevention and treatment of malignant tumor development and invasion, treatment of diseases of the cardiovascular system treatment of respiratory diseases, and treatment of diseases of nervous system. 
     
     
         6 . The compound of  claim 2  wherein the compound is prepared as a medicament for at least one of treatment of malignant tumors, prevention and treatment of malignant tumor development and invasion, treatment of diseases of the cardiovascular system, treatment of respiratory diseases, and treatment of diseases of nervous system. 
     
     
         7 . The compound of  claim 1  wherein the compound inhibits a function of Cdc42. 
     
     
         8 . The compound of  claim 7  wherein the function of Cdc42 is selected from the group consisting of cell movement, cell adhesion, apoptosis, intracellular transport, cytoskeletal reorganization, cellular endocytosis, regulation of cell cycle, cell transcription, and combinations thereof. 
     
     
         9 . The compound of  claim 2  wherein the compound inhibits a function of Cdc42. 
     
     
         10 . The compound of  claim 9  wherein the function of Cdc42 is selected from the group consisting of cell movement, cell adhesion, apoptosis, intracellular transport, cytoskeletal reorganization, cellular endocytosis, regulation of cell cycle, cell transcription, and combinations thereof. 
     
     
         11 . A pharmaceutical composition comprising a compound of  claim 1  and at least one excipient. 
     
     
         12 . A pharmaceutical composition comprising a compound of  claim 2  and at least one excipient. 
     
     
         13 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 13  wherein the compound is prepared as a medicament for at least one of treatment of malignant tumors, prevention and treatment of malignant tumor development and invasion, treatment of diseases of the cardiovascular system, treatment of respiratory diseases, and treatment of diseases of nervous system. 
     
     
         15 . The compound of  claim 13  wherein the compound inhibits a function of Cdc42. 
     
     
         16 . The compound of  claim 15  wherein the function of Cdc42 is selected from the group consisting of cell movement, cell adhesion, apoptosis, intracellular transport, cytoskeletal reorganization, cellular endocytosis, regulation of cell cycle, cell transcription, and combinations thereof.