G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases

G protein-coupled receptors (GPCRs) are important, potential drug targets for the treatment of metabolic disorders, such as obesity. GPCRs crosstalk with several transducers, including heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. GPCR-biased agonism has raised the potential of no...

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Main Authors: Shengnan Shen, Qiwen Liao, Liwei Gu, Yongping Zhu, Yanqing Liu, Xinwei Zhang, Junzhe Zhang, Qiaoli Shi, Yuxiang Sun, Jigang Wang, Ligen Lin
Format: Article
Language:English
Published: Compuscript Ltd 2024-02-01
Series:Acta Materia Medica
Online Access:https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0041
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author Shengnan Shen
Qiwen Liao
Liwei Gu
Yongping Zhu
Yanqing Liu
Xinwei Zhang
Junzhe Zhang
Qiaoli Shi
Yuxiang Sun
Jigang Wang
Ligen Lin
author_facet Shengnan Shen
Qiwen Liao
Liwei Gu
Yongping Zhu
Yanqing Liu
Xinwei Zhang
Junzhe Zhang
Qiaoli Shi
Yuxiang Sun
Jigang Wang
Ligen Lin
author_sort Shengnan Shen
collection DOAJ
description G protein-coupled receptors (GPCRs) are important, potential drug targets for the treatment of metabolic disorders, such as obesity. GPCRs crosstalk with several transducers, including heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. GPCR-biased agonism has raised the potential of novel drug development to preferentially activate therapeutic signaling pathways over pathways that lead to unwanted side effects. The obesity epidemic and its metabolic complications continue to be a major global public health threat but effective treatments are limited. The accelerated development of structural techniques, like X-ray crystallography and cryo-electron microscopy, has paved the way to understanding how biased agonism measured at GPCRs results in specific downstream physiologic responses. Herein some well-validated GPCR targets are briefly summarized and several new and promising receptors for obesity treatment are outlined. This review highlights the significance of deciphering the role of GPCRs in obesity pathology and biased signaling for drug development. We anticipate the review will facilitate the development of novel GPCR-targeted anti-obesity drugs that lead to heightened therapeutic efficacy with decreased side effect profiles.
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institution Kabale University
issn 2737-7946
language English
publishDate 2024-02-01
publisher Compuscript Ltd
record_format Article
series Acta Materia Medica
spelling doaj-art-ff691603cecd4052bd61b8b36d583a932025-08-20T03:31:46ZengCompuscript LtdActa Materia Medica2737-79462024-02-0131314510.15212/AMM-2023-0041G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseasesShengnan ShenQiwen LiaoLiwei GuYongping ZhuYanqing LiuXinwei ZhangJunzhe ZhangQiaoli ShiYuxiang SunJigang WangLigen LinG protein-coupled receptors (GPCRs) are important, potential drug targets for the treatment of metabolic disorders, such as obesity. GPCRs crosstalk with several transducers, including heterotrimeric G proteins, GPCR kinases (GRKs), and β-arrestins. GPCR-biased agonism has raised the potential of novel drug development to preferentially activate therapeutic signaling pathways over pathways that lead to unwanted side effects. The obesity epidemic and its metabolic complications continue to be a major global public health threat but effective treatments are limited. The accelerated development of structural techniques, like X-ray crystallography and cryo-electron microscopy, has paved the way to understanding how biased agonism measured at GPCRs results in specific downstream physiologic responses. Herein some well-validated GPCR targets are briefly summarized and several new and promising receptors for obesity treatment are outlined. This review highlights the significance of deciphering the role of GPCRs in obesity pathology and biased signaling for drug development. We anticipate the review will facilitate the development of novel GPCR-targeted anti-obesity drugs that lead to heightened therapeutic efficacy with decreased side effect profiles.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0041
spellingShingle Shengnan Shen
Qiwen Liao
Liwei Gu
Yongping Zhu
Yanqing Liu
Xinwei Zhang
Junzhe Zhang
Qiaoli Shi
Yuxiang Sun
Jigang Wang
Ligen Lin
G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
Acta Materia Medica
title G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
title_full G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
title_fullStr G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
title_full_unstemmed G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
title_short G protein-coupled receptor-biased signaling: potential drug discovery to facilitate treatment of metabolic diseases
title_sort g protein coupled receptor biased signaling potential drug discovery to facilitate treatment of metabolic diseases
url https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2023-0041
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