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Discovery of SHR9352: A Highly Potent G Protein-Biased ?-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 ?-opioid receptor (MOR) agonist, SHR9352. This novel molecule exhibited excellent MOR activity and limited ?-arrestin recruitment, as well as a high selectivity over ?-opioid receptor and ?-opioid receptor demonstrated robust in vivo efficacy and displayed favorable pharmacokinetic properties across species.

SUBMITTER: Li X

PROVIDER: S-EPMC6645658 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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

Li Xin X He Wei W Chen Yang Y Yang Guimei G Wan Hong H Zhang Lei L Hu Qiyue Q Feng Jun J Zhang Zhigao Z He Feng F Bai Chang C Zhang Lianshan L You Li L Tao Weikang W

ACS omega 20171228 12

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 ro ...[more]

PMID: 31457439

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Carfentanil is a β-arrestin-biased agonist at the μ opioid receptor.

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