In Vitro, In Vivo and In Silico Characterization of a Novel Kappa-Opioid Receptor Antagonist.

ABSTRACT: Kappa-opioid receptor (KOR) antagonists are promising innovative therapeutics for the treatment of the central nervous system (CNS) disorders. The new scaffold opioid ligand, Compound A, was originally found as a mu-opioid receptor (MOR) antagonist but its binding/selectivity and activation profile at the KOR and delta-opioid receptor (DOR) remain elusive. In this study, we present an in vitro, in vivo and in silico characterization of Compound A by revealing this ligand as a KOR antagonist in vitro and in vivo. In the radioligand competitive binding assay, Compound A bound at the human KOR, albeit with moderate affinity, but with increased affinity than to the human MOR and without specific binding at the human DOR, thus displaying a preferential KOR selectivity profile. Following subcuta

SUBMITTER: Puls K 

PROVIDER: S-EPMC9229160 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature