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.

中文翻译：

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SHR9352的发现：高强度G蛋白偏置的μ阿片受体激动剂

近来，靶向G蛋白偏向的信号传导已经成为一种有吸引力的治疗策略，用于治疗严重的急性疼痛，具有减轻传统阿片类药物副作用的潜力。在这里，我们描述了一种高度有效的偏向G蛋白的μ阿片受体（MOR）激动剂SHR9352的发现。这种新颖的分子表现出出色的MOR活性和有限的β-arrestin募集，并且对κ阿片受体和δ阿片受体具有很高的选择性，表现出强大的体内功效，并在整个物种中显示出良好的药代动力学特性。