The progress of small molecules against cannabinoid 2 receptor (CB2R)

Abstract

The two subtypes of cannabinoid receptors (CBR), namely CB₁R and CB₂R, belong to the G protein-coupled receptor (GPCR) superfamily and are confirmed as potential therapeutic targets for a variety of diseases such as inflammation, neuropathic pain, and immune-related disorders. Since CB₁R is mainly distributed in the central nervous system (CNS), it could produce severe psychiatric adverse reactions and addiction. In contrast, CB₂R are predominantly distributed in the peripheral immune system with minimal CNS-related side effects. Therefore, more attention has been devoted to the discovery of CB₂R ligands. In view of the favorable profile of CB₂R, many high-binding affinity and selectivity CB₂R ligands have been developed recently. This paper reviews recent research progress on CB₂R ligands, including endogenous CB₂R ligands, natural compounds, and novel small molecules, in order to provide a reference for subsequent CB₂R ligand development.

Keywords: CB(2)R; Endogenous ligands; Natural compounds; Small molecules.