Referenced in: none

Automatically associated channels: HCN3

Title: Activation of CFTR by UCCF-029 and genistein.

Authors: Layla Al-Nakkash, Mark F Springsteel, Mark J Kurth, Michael H Nantz

Journal, date & volume: Bioorg. Med. Chem. Lett., 2008 Jul 15 , 18, 3874-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18595696

Abstract
The mechanism of action of a novel CFTR activator UC(CF)-029 on NIH3T3 cells stably expressing DeltaF508-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 (10microM) is approximately 50% that of genistein; however, the EC(50)'s for both drugs are comparable; 3.5microM for UC(CF)-029 and 4.4muM 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 DeltaF508-CFTR channel activity necessitates further interest.