Identification of novel ligands interacting with kappa opioid receptors

Abstract

Background The opioid (KOP) receptor belongs to the family of seven transmembrane G protein-coupled receptors (GPCRs) and it plays a significant role in a broad range of physiological functions. Stimulation of the KOP receptor results in analgesic actions, and KOP agonists appear to have some advantages over the μ opioid (MOP) receptor agonists. Inhibiting KOP receptors is proposed to be useful for treating addiction and stress-related conditions, such as depression and anxiety. The pharmacology of currently available KOP antagonists shows a delay in onset of action and an extremely long duration of action in vivo, which might limit their therapeutic application. The search for new ligands with potent biological activities, particularly as potential novel therapeutic agents, utilizing computational and synthetical approaches, is a key goal of life science research and drug development. Herein, we present the in silico, in vitro and in vivo profiles of new molecular scaffolds as novel KOP receptor ligands.