Activation of CFTR by UCCF-029 and genistein

The mechanism of action of a novel CFTR activator UCCF-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 UCCF-029 and genistein have differing efficacies. The efficacy of UCCF-029 in the presence of forskolin (10 μM) is not, vert, similar50% that of genistein; however, the EC50’s for both drugs are comparable; 3.5 μM for UCCF-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 UCCF-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 UCCF-029 to augment ΔF508-CFTR channel activity necessitates further interest.