Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cellpermeable fluorescent probe.

Gazzi, ThaisGrande Rodríguez, Mª TeresaNazare, MarcRomero, Julián2023-10-172023-10-1720222041-6520https://hdl.handle.net/10641/3469Despite 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.engAtribución-NoComercial-SinDerivadas 3.0 Españahttp://creativecommons.org/licenses/by-nc-nd/3.0/es/Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cellpermeable fluorescent probe.journal articleopen access10.1039/d1sc06659e