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

Although sigma-2 (sigma(2)) 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 sigma(2)-selective fluorescent tracer (compound 5) as a specific tool to study sigma(2) 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 sigma(2) receptors, avoiding the inconvenient use of radioligands. Comparison with a previously developed mixed sigma(1)/sigma(2) fluorescent tracer (1) also allowed for the detection of sigma(1) receptors within these cells. Results obtained by flow cytometry with tracers 1 and 5 were confirmed by standard methods (western blot for sigma(1), and Scatchard analysis for sigma(2) receptors). Thus, we have produced powerful new tools for research on the sigma whose reliability and adaptability to a number of fluorescence techniques will be useful to elucidate the roles of sigma receptors in oncology.