Discovery of SHR9352: A Highly Potent G Protein-Biased μ-Opioid Receptor Agonist

Abstract

Recently, targeting the G protein-biased signaling has emerged as an attractive therapeutic strategy for treating severe acute pain with the potential to reduce the side effect of the traditional opioid drug. Herein, we describe the discovery of a highly potent G protein-biased μ-opioid receptor (MOR) agonist, SHR9352. This novel molecule exhibited excellent MOR activity and limited β-arrestin recruitment, as well as a high selectivity over κ-opioid receptor and δ-opioid receptor demonstrated robust in vivo efficacy and displayed favorable pharmacokinetic properties across species.