Discovery of a Photoaffinity Probe that Captures the Active Conformation of the Cannabinoid CB2 Receptor

The cannabinoid receptor type 2 (CB 2 R) is a G protein‐coupled receptor with therapeutic potential for the treatment of inflammatory disorders. Fluorescent probes are desirable to study its receptor localization, expression and occupancy. Previously, we have reported a photoaffinity probe LEI‐121 that stabilized the inactive conformation of the CB 2 R. Here, we report the structure‐based design of a novel bifunctional probe that captures the active conformation of the CB 2 R upon irradiation with light. An alkyne handle was incorporated to visualize the receptor using click‐chemistry with fluorophore‐azides. These probes may hold promise to study different receptor conformations in relation to their cellular localization and function.