Correctors of protein trafficking defects identified by a novel high-throughput screening assay

Chembiochem. 2007 Jun 18;8(9):1012-20. doi: 10.1002/cbic.200700027.


High-throughput small-molecule screens hold great promise for identifying compounds with potential therapeutic value in the treatment of protein-trafficking diseases such as cystic fibrosis (CF) and nephrogenic diabetes insipidus (NDI). The approach usually involves expressing the mutant form of the gene in cells and assaying function in a multiwell format when cells are exposed to libraries of compounds. Although such functional assays are useful, they do not directly test the ability of a compound to correct defective trafficking of the protein. To address this we have developed a novel corrector-screening assay for CF, in which the appearance of the mutant protein at the cell surface is measured. We used this assay to screen a library of 2000 compounds and have isolated several classes of trafficking correctors that had not previously been identified. This novel screening approach to protein-trafficking diseases is robust and general, and could enable the selection of molecules that could be translated rapidly to a clinical setting.

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Membrane Permeability
  • Cricetinae
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
  • Drug Evaluation, Preclinical
  • Enzyme-Linked Immunosorbent Assay
  • Fluorescent Antibody Technique
  • Hemagglutinins / chemistry
  • Iodides / chemistry
  • Piperazines / chemistry
  • Proteins / chemistry*
  • Purines / chemistry
  • Sildenafil Citrate
  • Spectrometry, Fluorescence
  • Sulfones / chemistry
  • Tissue Fixation


  • Hemagglutinins
  • Iodides
  • Piperazines
  • Proteins
  • Purines
  • Sulfones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Sildenafil Citrate