| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1364963 | Bioorganic & Medicinal Chemistry Letters | 2008 | 4 Pages |
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 ∼50% 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.
Graphical abstractThe effects of UCCF-029 on CFTR are compared with genistein.Figure optionsDownload full-size imageDownload as PowerPoint slide
