High-throughput screening of libraries of compounds to identify CFTR modulators

Methods Mol Biol. 2011:741:13-21. doi: 10.1007/978-1-61779-117-8_2.

Abstract

Small molecules acting as selective activators (potentiators), inhibitors, or "correctors" of the CFTR chloride channel represent candidate drugs for various pathological conditions including cystic fibrosis and secretory diarrhea. The identification of CFTR pharmacological modulators may be achieved by screening highly diverse synthetic or natural compound libraries using high-throughput methods. A convenient assay for CFTR function is based on the halide sensitivity of the yellow fluorescent protein (YFP). CFTR activity can be simply assessed by measuring the rate of YFP signal decrease caused by iodide influx. This assay can be automated to test thousands of compounds per day.

MeSH terms

  • Cystic Fibrosis Transmembrane Conductance Regulator / agonists
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Drug Evaluation, Preclinical / methods*
  • HEK293 Cells
  • High-Throughput Screening Assays / methods*
  • Humans
  • Luminescent Proteins / genetics
  • Microscopy, Fluorescence
  • Mutation
  • Small Molecule Libraries / pharmacology*
  • Transfection

Substances

  • Luminescent Proteins
  • Small Molecule Libraries
  • Cystic Fibrosis Transmembrane Conductance Regulator