4-Chlorobenzo[F]isoquinoline (CBIQ), a novel activator of CFTR and DeltaF508 CFTR

Eur J Pharmacol. 2005 Jun 1;516(2):118-24. doi: 10.1016/j.ejphar.2005.04.037.


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 DeltaF508 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression
  • Humans
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Isoquinolines / pharmacology*
  • Membrane Potentials / drug effects
  • Microinjections
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Oocytes / physiology
  • Phenanthrolines / pharmacology
  • Potassium Channels, Calcium-Activated / genetics
  • Potassium Channels, Calcium-Activated / physiology
  • Quinolines / pharmacology
  • RNA, Complementary / administration & dosage
  • RNA, Complementary / genetics
  • Rats
  • Rats, Inbred F344
  • Thyroid Gland / cytology
  • Thyroid Gland / drug effects
  • Thyroid Gland / physiology
  • Xenopus laevis


  • 4-chlorobenzo(f)isoquinoline
  • CFTR protein, human
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Isoquinolines
  • KCNN4 protein, human
  • Phenanthrolines
  • Potassium Channels, Calcium-Activated
  • Quinolines
  • RNA, Complementary
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • 7,8-benzoquinoline