Functionalized Cannabinoid Subtype 2 Receptor Ligands: Fluorescent, PET, Photochromic and Covalent Molecular Probes

Cannabinoid subtype 2 receptors (CB₂ Rs) are G protein-coupled receptors (GPCRs) belonging to the endocannabinoid system, a complex network of signalling pathways leading to the regulation of key physiological processes. Interestingly, CB₂ Rs are strongly up-regulated in pathological conditions correlated with the onset of inflammatory events like cancer and neurodegenerative diseases. Therefore, CB₂ Rs represent an important biological target for therapeutic as well as diagnostic purposes. No CB₂ R-selective drugs are yet on the market, thus underlining a that deeper comprehension of CB₂ Rs' complex activation pathways and their role in the regulation of diseases is needed. Herein, we report an overview of pharmacological and imaging tools such as fluorescent, positron emission tomography (PET), photochromic and covalent selective CB₂ R ligands. These molecular probes can be used in vitro as well as in vivo to investigate and explore the unravelled role(s) of CB₂ Rs, and they can help to design suitable CB₂ R-targeted drugs.