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
2008-06-01
发表期刊ACTA PHARMACOLOGICA SINICA
ISSN1671-4083
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
DOI10.1111/j.1745-7254.2008.00800.x
收录类别SCI
语种英语
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000256441900015
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
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
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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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