Recent progress in assays for GPCR drug discovery
文献类型：期刊论文
| 作者 | Guo, Shimeng1; Zhao, Tingting2; Yun, Ying3; Xie, Xin1,2,3,4
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| 刊名 | AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
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| 出版日期 | 2022-08-01 |
| 卷号 | 323期号:2页码:C583-C594 |
| 关键词 | biased signaling GPCR high -throughput screening assays humanized mouse model protein protein interaction |
| ISSN号 | 0363-6143 |
| DOI | 10.1152/ajpcell.00464.2021 |
| 通讯作者 | Xie, Xin(xxie@simm.ac.cn) |
| 英文摘要 | G-protein-coupled receptors (GPCRs), also known as seven transmembrane receptors, are the largest family of cell surface receptors in eukaryotes. There are -800 GPCRs in human, regulating diverse physiological processes. The GPCRs are the most intensively studied drug targets. Drugs that target GPCRs account for about a quarter of the global market share of therapeutic drugs. Therefore, to develop physiologically relevant and robust assays to search new GPCR ligands or modulators remain the major focus of drug discovery research worldwide. Early functional GPCR assays mainly depend on the measurement of G-protein-mediated second messenger generation. Recent developments in GPCR biology indicate that the signaling of these receptors is much more complex than the oversimplified classical view. The GPCRs have been found to activate multiple G proteins simultaneously and induce b-arrestin-mediated signaling. They have also been found to interact with other cytosolic scaffolding proteins and form dimer or heteromer with GPCRs or other transmembrane proteins. Here, we mainly discuss technologies focused on detecting protein-protein interactions, such as fluorescence resonance energy transfer/bioluminescence resonance energy transfer (FRET/BRET), NanoLuc binary technology (NanoBiT), Tango, etc., and their applications in measuring GPCRs interacting with various signaling partners. In the final part, we also discuss the species differences in GPCRs when using animal models to study the in vivo functions of GPCR ligands, and possible ways to solve this problem with modern genetic tools. |
| WOS关键词 | PROTEIN-COUPLED-RECEPTOR ; RESONANCE ENERGY-TRANSFER ; MU-OPIOID RECEPTOR ; SEVERE ACUTE PAIN ; LIVE CELLS ; ACTIVATION ; COMPLEMENTATION ; OLICERIDINE ; REVEALS ; BINDING |
| 资助项目 | National Natural Science Foundation of China[82121005] ; National Natural Science Foundation of China[81730099] ; National Natural Science Foundation of China[82030109] ; Ministry of Science and Technology China Brain Initiative[2022ZD0204701] ; Shanghai Municipal Science and Technology Major Projects[TM202101H005] ; Shanghai Municipal Science and Technology Major Projects[20S11903200] |
| WOS研究方向 | Cell Biology ; Physiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000889459900005 |
| 出版者 | AMER PHYSIOLOGICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304533]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xie, Xin |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 3.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou, Peoples R China 4.Shanghai Inst Mat Med, Chinese Acad Sci, State Key Lab Drug Res, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Shimeng,Zhao, Tingting,Yun, Ying,et al. Recent progress in assays for GPCR drug discovery[J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,2022,323(2):C583-C594. |
| APA | Guo, Shimeng,Zhao, Tingting,Yun, Ying,&Xie, Xin.(2022).Recent progress in assays for GPCR drug discovery.AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY,323(2),C583-C594. |
| MLA | Guo, Shimeng,et al."Recent progress in assays for GPCR drug discovery".AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 323.2(2022):C583-C594. |
入库方式： OAI收割
来源：上海药物研究所
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