Methods for identifying compounds for inhibition of neoplastic lesions, and pharmacetical compositions containing such compounds

Abstract

This invention provides pharmaceutical compositions containing compounds 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 prefereably not substantial prostaglandin inhibitory activity, are desirable for the treatment of neoplasia.

We claim:  
     
         1  A method of treating neoplasia in a patient, comprising administering to the patient a pharmacologically effective amount of a compound selected by: 
 determining COX inhibitory activity of the compound, and  
 determining PDE-5 inhibitory activity of said compound,  
 wherein the compound that is selected for administration to the patient inhibits COX activity no more than 25% at a concentration of 100 uM and inhibits PDE-5 activity to a greater extent than exisulind, with the proviso that the compound is not sulindac or sulindac sulfide; and  
 providing written material to the patient describing said compound as having PDE-5 inhibitory activity.  
 
     
     
         2 . A method for treating neoplasia in a patient, wherein said neoplasia is selected from the group consisting of colo-rectal, breast and prostate neoplasia, comprising 
 administering to a patient a pharmacologically effective amount of a compound selected by: 
 determining COX inhibitory activity of the compound, and  
 determining PDE-5 inhibitory activity of said compound,  
 wherein the compound that is selected for administration to the patient inhibits COX activity no more than 25% at a concentration of 100 uM and inhibits PDE-5 activity to a greater extent than exisulind, with the proviso that the compound is not sulindac or sulindac sulfide.; and  
   providing written material to the patient describing said compound as having PDE-5 inhibitory activity.