Activation of CFTR by UCCF-029 and genistein

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

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3874-3877
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume18
Issue number14
DOIs
StatePublished - Jul 15 2008

Keywords

  • CFTR
  • Genistein
  • Pharmacological activators
  • UC-029

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Medicine(all)

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    Al-Nakkash, L., Springsteel, M. F., Kurth, M. J., & Nantz, M. H. (2008). Activation of CFTR by UCCF-029 and genistein. Bioorganic and Medicinal Chemistry Letters, 18(14), 3874-3877. https://doi.org/10.1016/j.bmcl.2008.06.051