Open AccessDiscovery of SHR9352: A Highly Potent G Protein-Biased μ-Opioid Receptor Agonist
Author(s) -
Xin Li,
Wei He,
Yang Chen,
Guimei Yang,
Hong Wan,
Lei Zhang,
Qiyue Hu,
Jun Feng,
Zhigao Zhang,
Feng He,
Chang Bai,
Lianshan Zhang,
Li You,
Weikang Tao
Publication year - 2017
Publication title -
acs omega
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.779
H-Index - 40
ISSN - 2470-1343
DOI - 10.1021/acsomega.7b01452
Subject(s) - agonist , functional selectivity , pharmacology , opioid , receptor , opioid receptor , g protein coupled receptor , drug discovery , chemistry , arrestin , medicine , biochemistry
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.