Activation of CFTR by UCCF-029 and genistein |
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| Authors: | Al-Nakkash Layla Springsteel Mark F Kurth Mark J Nantz Michael H |
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| Institution: | aDepartment of Physiology, Midwestern University, 19555 N 59th Avenue, Glendale, AZ 85308, USA;bDepartment of Chemistry, Sierra College, Rocklin, CA 95677, USA;cDepartment of Chemistry, University of California Davis, CA 95616-5295, USA;dDepartment of Chemistry, University of Louisville, Louisville, KY 40292, USA |
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| Abstract: | 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. |
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| Keywords: | CFTR Genistein UCCF-029 Pharmacological activators |
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