Protein tyrosine kinase inhibitors for treating osteoarthritis

Abstract

Disclosed is a method of treating an individual or animal with osteoarthritis. The method comprises administering to the individual or animal a therapeutically effective amount of a protein tyrosine kinase inhibitor.

What is claimed is:  
     
         1 . A method of treating an individual or animal with osteoarthritis comprising administering to the individual or animal a therapeutically effective amount of a protein tyrosine kinase inhibitor, with the proviso that the protein tyrosine kinase inhibitor is not a flavone, isoflavone, hymenialdisine or hymenialdisine analogue.  
     
     
         2 . The method of  claim 1  wherein the protein tyrosine kinase inhibitor inhibits interleukin-1 stimulated cartilage degradation in chondrocytes in cell culture.  
     
     
         3 . The method of  claim 1  wherein the protein tyrosine kinase inhibitor inhibits interleukin-1 stimulated biosynthesis of matrix metalloproteinase enzymes in chondrocytes in cell culture.  
     
     
         4 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is represented by the following structural formula:  
       
         
           
           
               
               
           
         
         wherein: 
 m is one or two;  
 R 1  is —H, —OH or —OMe;  
 R 2  is —H or —CN; and  
 R 1  is —H, —NO 2 , halogen or an organic radical.  
 
       
     
     
         5 . The method of  claim 4  wherein the protein tyrosine kinase inhibitor is represented by the folowing structural formula:  
       
         
           
           
               
               
           
         
       
     
     
         6 . The method of  claim 4  wherein the protein tyrosine kinase inhibitor is selected from the group consisting of tyrphostin AG 556 and tyrphostin AG82.  
     
     
         7 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is represented by the following structural formula:  
       
         
           
           
               
               
           
         
         wherein R 3 -R 6  are each independently selected from the group consisting of —H, —Cl, —OH and —OMe.  
       
     
     
         8 . The method of  claim 7  wherein the protein tyrosine kinase is 4,5-dianilinophthalimide (DAPH).  
     
     
         9 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is a compound represented by a structure selected from the group consisting of:  
       
         
           
           
               
               
           
         
         wherein: 
 n is one, two or three; and  
 R III  and R V  are each an organic radical.  
 
       
     
     
         10 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is herbimycin A.  
     
     
         11 . The method of  claim 1  wherein the protein tyrosine kinase inhibitor inhibits interleukin-1 stimulated cartilage degradation in a cartilage explant assay.  
     
     
         12 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is represented by the following structural formula:  
       
         
           
           
               
               
           
         
         wherein: 
 m is one or two;  
 R 1  is selected from the group consisting of —H, —OH and —OMe;  
 R 2  is —H or —CN; and  
 p is an integer from one to eight.  
 
       
     
     
         13 . The method of  claim 2  wherein the protein tyrosine kinase inhibitor is a tyrphostin.  
     
     
         14 . The method of  claim 1  wherein the protein tyrosine kinase inhibitor inhibits interleukin-1 stimulated aggrecanase activity by chondrocytes in cell culture.