Synthesis and pharmacological validation of a novel radioligand for the orphan GPR88 receptor.
Fiche publication
Date publication
janvier 2023
Journal
Bioorganic & medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DARCQ Emmanuel
Tous les auteurs :
Decker AM, Rahman MT, Kormos CM, Hesk D, Darcq E, Kieffer BL, Jin C
Lien Pubmed
Résumé
GPR88 is an orphan G protein-coupled receptor which has been implicated in a number of striatal-associated disorders. Herein we describe the synthesis and pharmacological characterization of the first GPR88 radioligand, [H]RTI-33, derived from a synthetic agonist RTI-13951-33. [H]RTI-33 has a specific activity of 83.4 Ci/mmol and showed one-site, saturable binding (K of 85 nM) in membranes prepared from stable PPLS-HA-hGPR88-CHO cells. A competition binding assay was developed to determine binding affinities of several known GPR88 agonists. This radioligand represents a powerful tool for future mechanistic and cell-based ligand-receptor interaction studies of GPR88.
Mots clés
GPR88, Radioligand binding, [(3)H]RTI-33
Référence
Bioorg Med Chem Lett. 2023 01 15;80:129120