Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe

Our medicinal chemistry partner site, the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin, Germany, has collaborated with 17 leading research institutions and pharma companies in Europe and the USA to develop a CB2R probe and its validation in different laboratories. Read more about their discoveries in the recent publication in Chemical Science.

Despite its essential role in the (patho)physiology of several diseases, CB2R tissue expression profiles and signaling mechanisms are not yet fully understood. We report the development of a highly potent, fluorescent CB2R agonist probe employing structure-based reverse design. It commences with a highly potent, preclinically validated ligand, which is conjugated to a silicon-rhodamine fluorophore, enabling cell permeability. The probe is the first to preserve interspecies affinity and selectivity for both mouse and human CB2R. Extensive cross-validation (FACS, TR-FRET and confocal microscopy) set the stage for CB2R detection in endogenously expressing living cells along with zebrafish larvae. Together, these findings will benefit clinical translatability of CB2R based drugs. For more information please read the full publication DOI: 10.1039/D1SC06659E here.