Activation of CFTR by UCCF-029 and genistein

Abstract The mechanism of action of a novel CFTR activator UC CF -029 on NIH3T3 cells stably expressing ΔF508-CFTR was investigated and its effects compared to those of genistein, a known CFTR activator. This study shows that UC CF -029 and genistein have differing efficacies. The efficacy of UC CF -029 in the presence of forskolin (10 μM) is ∼50% that of genistein; however, the EC 50 ’s for both drugs are comparable; 3.5 μM for UC CF -029 and 4.4 μM for genistein. Using NIH3T3 cells stably transfected with K1250A-CFTR we find that CFTR channel open time is unaffected by UC CF -029 or genistein, supporting the hypothesis that these compounds stabilize the open state by inhibiting ATP hydrolysis at NBD2. Our data suggest that the ability of UC CF -029 to augment ΔF508-CFTR channel activity necessitates further interest.