Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists
文献类型：期刊论文
| 作者 | Jia, Yuxin2,3; Liu, Meiying1; Xu, Heng2; Zhang, Yixin2 |
| 刊名 | CURRENT PHARMACEUTICAL DESIGN
 |
| 出版日期 | 2025 |
| 卷号 | 31期号:37页码:3017-3027 |
| 关键词 | TRPV4 GSK101 LM0038 mechanical pain acute itch sensory response |
| ISSN号 | 1381-6128 |
| DOI | 10.2174/0113816128381222250428094819 |
| 通讯作者 | Zhang, Yixin(yxzhang6688@163.com) |
| 英文摘要 | Aims We aimed to synthesize small-molecule compounds by modifying the chemical structure of GSK101 and screening for novel TRPV4 agonists with high specificity and selective sensory response.Background GSK1016790A (GSK101) effectively activates Transient Receptor Potential Vanilloid 4 (TRPV4) and simultaneously induces mechanical allodynia and acute itch. However, as a commonly used tool compound for studying sensory function, its dual effects of pain and itch can interfere with each other.Objective To design and synthesize a series of small-molecule compounds targeting TRPV4, evaluate their properties to identify the most specific tool compounds targeting TRPV4, and determine the correlation between TRPV4 activation and sensory response.Methods In this study, live-cell Ca2+ imaging in a heterogeneous expression system was employed to evaluate the activity of synthetic compounds, molecular docking was performed to predict binding interactions and behavioral tests for itch and pain were combined with pharmacological and genetic strategies to assess physiological responses.Results We synthesized nine GSK101 analogues and identified six small-molecule agonists that exhibited TRPV4-targeting excitability, preserved TRPV4-mediated mechanical pain perception, and attenuated the acute itch response.Conclusion Our study provides new insight into the role of TRPV4 in pain and itch sensation and introduces LM0038, the most potent agonist, as a novel alternative to GSK101. With enhanced biological activity, it may serve as a valuable tool for studying TRPV4 function. |
| WOS关键词 | CHANNEL TRPV4 ; THERAPEUTIC TARGET ; ION-CHANNEL ; PAIN ; MODULATION ; ACTIVATION ; ITCH |
| 资助项目 | National Natural Science Foundation of China[81772098] ; National Natural Science Foundation of China[82002064] ; Shanghai Sailing Program[20YF1422700] ; Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support[20152227] ; Clinical Research Project of Health Industry of Shanghai Health Committee[20224Y0146] ; Shanghai Rising Stars of Medical Talents Youth Development Program[2022-26] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001560214700005 |
| 出版者 | BENTHAM SCIENCE PUBL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321375]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhang, Yixin |
| 作者单位 | 1.Chinese Acad Sci, Ctr Chem Biol, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Plast & Reconstruct Surg, Sch Med, Shanghai 200011, Peoples R China 3.Capital Med Univ, Beijing Childrens Hosp, Dept Burn & Plast Surg, Beijing 100045, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jia, Yuxin,Liu, Meiying,Xu, Heng,et al. Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists[J]. CURRENT PHARMACEUTICAL DESIGN,2025,31(37):3017-3027. |
| APA | Jia, Yuxin,Liu, Meiying,Xu, Heng,&Zhang, Yixin.(2025).Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists.CURRENT PHARMACEUTICAL DESIGN,31(37),3017-3027. |
| MLA | Jia, Yuxin,et al."Identification of Novel Selective Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists".CURRENT PHARMACEUTICAL DESIGN 31.37(2025):3017-3027. |
入库方式： OAI收割
来源：上海药物研究所
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