Method for identifying compounds for inhibition of neoplastic lesions

Abstract

This invention provides a method to identify compounds potentially useful for the treatment of neoplasia in mammals. The phosphodiesterase inhibitory activity of a compound is determined along with COX inhibitory activity. Growth inhibitory and apoptosis inducing effects on cultured tumor cells are also determined. Compounds that exhibit phosphodiesterase inhibiton, growth inhibition and apoptosis induction, but not substantial prostaglandin inhibitory activity, are desirable for the treatment of neoplasia.

We claim:  
     
         1 . A method for identifying a compound with potential for treating neoplasia, comprising: 
 treating neoplastic cells with the compound to be evaluated at a concentration between about 200 μM to 200 pM;    determining the intracellular amount of cGMP in the treated cells; determining the intracellular amount of cAMP in the treated cells;    wherein about a three-fold or greater increase in the ratio of cGMP/cAMP in the treated cells compared to the ratio of cGMP/cAMP in untreated neoplastic cells is indicative that the compound has potential for treating neoplasia.    
     
     
         2 . The method of  claim 1  wherein an intracellular amount of cGmp in the treated cells greater than 500 fmol/mg protein is indicative that the compound has potential for treating neoplasia.  
     
     
         3 . The method of  claim 1  wherein an intracellular amount of cAMP in the treated cells less than 4000 fmol/mg protein is indicative that the compound has potential for treating neoplasia.  
     
     
         4 . The method of  claim 3  wherein an intracellular amount of cAMP in the treated cells less than 4000 fmol/mg protein is indicative that the compound has potential for treating neoplasia.