Novel and Selective Fluorescent σ2 -Receptor Ligand with a 3,4-Dihydroisoquinolin-1-one Scaffold: A Tool to Study σ2 Receptors in Living Cells

Chembiochem. 2015 May 4;16(7):1078-83. doi: 10.1002/cbic.201402712. Epub 2015 Mar 10.


Although sigma-2 (σ2 ) receptors are still enigmatic proteins, they are promising targets for tumor treatment and diagnosis. With the aim of clarifying their role in oncology, we developed a σ2 -selective fluorescent tracer (compound 5) as a specific tool to study σ2 receptors. By using flow cytometry with 5, we performed competition binding studies on three different cell lines where we also detected the content of the σ2 receptors, avoiding the inconvenient use of radioligands. Comparison with a previously developed mixed σ1 /σ2 fluorescent tracer (1) also allowed for the detection of σ1 receptors within these cells. Results obtained by flow cytometry with tracers 1 and 5 were confirmed by standard methods (western blot for σ1 , and Scatchard analysis for σ2 receptors). Thus, we have produced powerful new tools for research on the σ whose reliability and adaptability to a number of fluorescence techniques will be useful to elucidate the roles of σ receptors in oncology.

Keywords: cancer; flow cytometry; fluorescent probes; ligand design; sigma receptors.

MeSH terms

  • Cell Survival
  • Drug Design*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism*
  • Humans
  • Isoquinolines / chemical synthesis
  • Isoquinolines / chemistry*
  • Isoquinolines / metabolism*
  • Protein Binding
  • Receptors, sigma / metabolism*
  • Substrate Specificity


  • Fluorescent Dyes
  • G 1616
  • Isoquinolines
  • Receptors, sigma