| High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1 | |
Yan, Jian-hua1,2; Li, Qun-yi1,2; Boutin, Jean A.3; Renard, M. Pierre3; Ding, Yi-xiang4; Hao, Xiao-jiang5 ; Zhao, Wei-min1,2; Wang, Ming-wei1,2
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| 通讯作者 | wangmw@mail.shcnc.ac.cn |
| 2008-06-01 | |
| 发表期刊 | ACTA PHARMACOLOGICA SINICA
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| ISSN | 1671-4083 |
| 卷号 | 29期号:6页码:752-758 |
| 摘要 | Aim: To find new antagonists on human melanin-concentrating hormone recep-tor-1 (MCHR-1) through high-throughput screening (HTS) of a diverse compound library. Methods: MCHR-1, [(3)H]SNAP7941, and FlashBlue G-protein-coupled receptor beads were used to measure the receptor-binding activities of various compounds based on scintillation proximity assay (SPA) technology. The guanosine 5' (gamma-[(35)S]thio) triphosphate ([(35)S]GTP gamma S) binding assay was subsequently applied to functionally characterize the "hits" identified by the HTS campaign. Results: Of the 48 240 compounds screened with the SPA method, 12 hits were confirmed to possess MCHR-1 binding activities, 8 were functionally studied subsequently with the [(35)S]GTP gamma S binding assay, and only 1 compound (NC127816) displayed moderate human MCHR-1 binding affinity (K(i)=115.7 nmol/L) and relatively potent antagonism (K(B)=23.8 nmol/L). This compound shares a novel scaffold (1-ethoxy-2H-2-aza-1-phospha-naphthalene 1-oxide) with 3 other analogs in the group. Conclusion: Considering the marked difference in molecular shape and electrostatic status between NC127816 and the structures reported elsewhere, we anticipate that its derivatives may represent a new class of potent MCHR-1 modulators. |
| 关键词 | Melanin-concentrating Hormone Melanin-concentrating Hormone Receptor-1 Antagonist |
| 学科领域 | Chemistry, Multidisciplinary ; Pharmacology & Pharmacy |
| DOI | 10.1111/j.1745-7254.2008.00800.x |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000256441900015 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/2929 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab New Drug Res, Shanghai 201203, Peoples R China 3.Les Labs Servier, F-92200 Neuillly Sur Seine, France 4.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, Peoples R China 5.Chinese Acad Sci, Kunming Inst Bot, Kunming 650204, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yan, Jian-hua,Li, Qun-yi,Boutin, Jean A.,et al. High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1[J]. ACTA PHARMACOLOGICA SINICA,2008,29(6):752-758. |
| APA | Yan, Jian-hua.,Li, Qun-yi.,Boutin, Jean A..,Renard, M. Pierre.,Ding, Yi-xiang.,...&Wang, Ming-wei.(2008).High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1.ACTA PHARMACOLOGICA SINICA,29(6),752-758. |
| MLA | Yan, Jian-hua,et al."High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1".ACTA PHARMACOLOGICA SINICA 29.6(2008):752-758. |
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