Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening

Abstract

Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for non-addictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result, and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain.