4-Chlorobenzo[F]isoquinoline (CBIQ), a novel activator of CFTR and ΔF508 CFTR

Meena Murthy, Nicoletta Pedemonte, Lesley MacVinish, Luis Galietta, Alan Cuthbert

Research output: Contribution to journalArticle

Abstract

4-Chlorobenzo[F]isoquinoline (CBIQ) is a novel compound, here shown to activate both CFTR (cystic fibrosis transmembrane conductance regulator) Cl - ion channels and KCNN4, intermediate conductance, calcium-sensitive K+-channels, present in transporting epithelia by the use of heterologous expression systems. Earlier studies with other benzoquinolines, namely 7,8- and 5,6 benzoquinoline, showed they too could activate CFTR and KCNN4, but the evidence was only indirect. However this study also shows that CBIQ can also activate ΔF508 CFTR, the most common mutant form of CFTR present in approximately 75% of patients with cystic fibrosis. This property is not shared with the other benzoquinolines. As activation of CFTR and KCNN4 work in unison to promote epithelial chloride secretion, CBIQ is a new chemical scaffold for developing agents that may be useful in cystic fibrosis.

Original languageEnglish
Pages (from-to)118-124
Number of pages7
JournalEuropean Journal of Pharmacology
Volume516
Issue number2
DOIs
Publication statusPublished - Jun 1 2005

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Keywords

  • CFTR (Cystic fibrosis transmembrane conductance regulator)
  • Chloride channel
  • Chloride secretion
  • Cystic fibrosis
  • Intermediate conductance calcium-sensitive potassium channel
  • KCNN4

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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