High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1
文献类型：期刊论文
| 作者 | Yan, Jian-hua2,4; Li, Qun-yi2,4; Boutin, Jean A.1; Renard, M. Pierre1; Ding, Yi-xiang5; Hao, Xiao-jiang3; Zhao, Wei-min2,4 ; Wang, Ming-wei2,4
|
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2008-06 |
| 卷号 | 29期号:6页码:752-758 |
| 关键词 | melanin-concentrating hormone melanin-concentrating hormone receptor-1 antagonist |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2008.00800.x |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | PROTEIN-COUPLED RECEPTOR ; HUMAN MCH RECEPTOR ; MESSENGER-RNA ; MOLECULAR CHARACTERIZATION ; FEEDING-BEHAVIOR ; MEDIAN-EMINENCE ; SLC-1 RECEPTOR ; BINDING ASSAY ; FEMALE RAT ; ALPHA-MSH |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:3301353 |
| WOS记录号 | WOS:000256441900015 |
| 出版者 | SHANGHAI INST MATERIA MEDICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272899]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, Ming-wei |
| 作者单位 | 1.Les Labs Servier, F-92200 Neuillly Sur Seine, France; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Kunming Inst Bot, Kunming 650204, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab New Drug Res, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Organ Chem, Shanghai 200032, 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. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。