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 (s2) 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 s2-selective fluorescent tracer compound 5) as a specific tool to study s2 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 s2 receptors, avoiding the inconvenient use of radioligands. Comparison with a previously developed mixed s1/s2 fluorescent tracer (1) also allowed for the detection of s1 receptors within these cells. Results obtained by flow cytometry with tracers 1 and 5 were confirmed by standard methods (western blot for s1, and Scatchard analysis for s2 receptors). Thus, we have produced powerful new tools for research on the s whose reliability and adaptability to a number of fluorescence techniques will be useful to elucidate the roles of s receptors in oncology.