Review of Voltage-gated Calcium Channel alpha 2 delta Subunit Ligands for the Treatment of Chronic Neuropathic Pain and Insight into Structure-activity Relationship (SAR) by Pharmacophore Modeling
文献类型：期刊论文
| 作者 | Chen, Yuting3; Wu, Qingqing3; Jin, Zhengsheng3; Qin, Yanlan3; Meng, Fancui2; Zhao, Guilong1,3 |
| 刊名 | CURRENT MEDICINAL CHEMISTRY
 |
| 出版日期 | 2022 |
| 卷号 | 29期号:30页码:5097-5112 |
| 关键词 | Voltage-gated calcium channel alpha 2 delta subunit neuropathic pain structure-activity relationship (SAR) pharmacophore modeling gabapentinoids |
| ISSN号 | 0929-8673 |
| DOI | 10.2174/0929867329666220407093727 |
| 通讯作者 | Meng, Fancui(mengfc@tjpr.com) ; Zhao, Guilong(zhao_guilong@126.com) |
| 英文摘要 | Background: Neuropathic pain (NP) is a complex symptom related to nerve damage. The discovery of new drugs for treating chronic NP has been continuing for several decades, while more progress is still needed because of the unsatisfactory efficacy and the side effects of the currently available drugs. Among all the approved drugs for chronic NP, voltage-gated calcium channel (VGCC) alpha 2 delta subunit ligands, also known as gabapentinoids, are among the first-line treatment and represent a class of efficacious and relatively safe therapeutic agents. However, new strategies are still needed to be explored due to the unsatisfied response rate. Objective: The aim of the study is to review the latest status of the discovery and development of gabapentinoids for the treatment of chronic NP by covering both the marketed and the preclinical/clinical ones. Moreover, it aims to analyze the structure-activity relationship (SAR) of gabapentinoids to facilitate the future design of structurally novel therapeutic agents targeting the VGCC alpha 2 delta subunit. Methods: We searched PubMed Central, Embase, Cochrane Library, Web of Science, Scopus, and Espacenet for the literature and patents on diabetic peripheral neuropathic pain, postherpetic neuralgia, fibromyalgia, voltage-gated calcium channel alpha 2 delta subunit and related therapeutic agents from incipient to June 10, 2021. The SAR of gabapentinoids was analyzed by pharmacophore modeling using the Phase module in the Schrodinger suite. Results: A variety of gabapentinoids were identified as VGCC alpha 2 delta ligands that have ever been under development to treat chronic NP. Among them, four gabapentinoids are marketed, one is in the active late clinical trials, and eight have been discontinued. Pharmacophore models were generated using the phase module in the Schrodinger suite, and common pharmacophores were predicted based on pharmacophoric features and analyzed. Conclusion: The latest progress in the discovery and development of gabapentinoids for the treatment of chronic NP was reviewed. Moreover, the structure-activity relationship (SAR) of gabapentinoids has been analyzed by pharmacophore modeling, which will be valuable for the future design of structurally novel therapeutic agents targeting the VGCC alpha 2 delta subunit. |
| WOS关键词 | AMINOMETHYL)-1-CYCLOHEXANE ACETIC-ACID ; DIABETIC PERIPHERAL NEUROPATHY ; ADULTS SEEKING TREATMENT ; POSTHERPETIC NEURALGIA ; ALPHA(2)DELTA LIGAND ; CLINICAL PHARMACOKINETICS ; GABAPENTIN PRODRUG ; RENAL IMPAIRMENT ; OPEN-LABEL ; MIROGABALIN |
| 资助项目 | Guangdong Provincial Natural Science Foundation[2021A1515010197] ; Zhongshan Municipal Natural Science Foundation[200805173640573] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000863520100005 |
| 出版者 | BENTHAM SCIENCE PUBL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/302742]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Meng, Fancui; Zhao, Guilong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 2.Tianjin Inst Pharmaceut Res, 308 Huiren Ave, Tianjin 300301, Peoples R China 3.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Yuting,Wu, Qingqing,Jin, Zhengsheng,et al. Review of Voltage-gated Calcium Channel alpha 2 delta Subunit Ligands for the Treatment of Chronic Neuropathic Pain and Insight into Structure-activity Relationship (SAR) by Pharmacophore Modeling[J]. CURRENT MEDICINAL CHEMISTRY,2022,29(30):5097-5112. |
| APA | Chen, Yuting,Wu, Qingqing,Jin, Zhengsheng,Qin, Yanlan,Meng, Fancui,&Zhao, Guilong.(2022).Review of Voltage-gated Calcium Channel alpha 2 delta Subunit Ligands for the Treatment of Chronic Neuropathic Pain and Insight into Structure-activity Relationship (SAR) by Pharmacophore Modeling.CURRENT MEDICINAL CHEMISTRY,29(30),5097-5112. |
| MLA | Chen, Yuting,et al."Review of Voltage-gated Calcium Channel alpha 2 delta Subunit Ligands for the Treatment of Chronic Neuropathic Pain and Insight into Structure-activity Relationship (SAR) by Pharmacophore Modeling".CURRENT MEDICINAL CHEMISTRY 29.30(2022):5097-5112. |
入库方式： OAI收割
来源：上海药物研究所
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