IDENTIFICATION OF NOVEL COMPOUNDS FOR THE PHARMACOLOGICAL CORRECTION OF CYSTIC FIBROSIS CHLORIDE TRANSPORT DEFECT

Cystic fibrosis (CF) is a severe inherited disorder which causes a progressive and irreversible damage to the lungs, pancreas, and other organs. The disease is caused by mutations that block chloride transport in epithelial cells. To date, no effective therapy has been identified to correct the CF defect. It is believed that the discovery of new drugs for CF may be obtained by screening a large number of organic compounds with an automated assay. The drugs found with this approach have to be studied in detail to confirm their ability to induce chloride transport in CF cells. In collaboration with investigators of the University of California at San Francisco and Davis we plan to perform primary and secondary screenings to identify new drugs. These drugs will be tested in different types of experiments to verify the amount of correction that can be obtained. The structure of the best compounds will be evaluated to design and synthesize new compound that could have improved characteristics. These new drugs could be evaluated to assess if they warrant consideration for animal testing and ultimately clinical trials.