Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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外文摘要：Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical practice.Unfortunately,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse reactions.As G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and des-cending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allo-steric modulation theory is gaining momentum.Extensive research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse effects.This review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the po-tential benefits and adverse factors of this treatment.We will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased agonists.It is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

外文关键词：

Neuropathic painAllosteric modulatorsG protein-coupled receptorsAnalgesia

作者：

Chunhao Zhu、Xiaobing Lan、Zhiqiang Wei、Jianqiang Yu、Jian Zhang

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作者单位：

School of Pharmacy,Ningxia Medical University,Yinchuan 750004,China

School of Basic Medical Science,Ningxia Medical University,Yinchuan 750004,China

Medicinal Chemistry and Bioinformatics Center,Ocean University of China,Qingdao 266100,China

Medicinal Chemistry and Bioinformatics Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210023,China

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基金：

国家自然科学基金国家自然科学基金Innovation Program of Shanghai Municipal Education CommissionKey Research and Development Program of Ningxia Hui Autonomous RegionInnovative Research Team of High-level Local Universities in ShanghaiInnovative Research Team of High-level Local Universities in Shanghai宁夏回族自治区自然科学基金宁夏回族自治区自然科学基金Starry Night Science Fund of Zhejiang University Shanghai Institute for Advanced Studyopen fund of state key laboratory of Pharmaceutical Biotechnology,Nanjing University

项目编号：

81925034222370052019-01-07-00-01-E000362022CMG01002SSMU-ZLCX20180702SHSMU-ZDCX202127002022AAC020292021AAC03139SN-ZJU-SIAS-007KF-202204

出版年：

2024

DOI：

10.1016/j.apsb.2023.07.020

药学学报(英文版)

CSTPCD

ISSN：

年,卷(期)：2024.14(1)

参考文献量161