Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139
文献类型：期刊论文
| 作者 | Shi, Feng2; Shen, Jing Kang2; Chen, Danqi2 ; Fog, Karina1; Thirstrup, Kenneth1; Hentzer, Morten1; Karlsson, Jens-Jakob1; Menon, Veena3; Jones, Kenneth A.3; Smith, Kelli E.3
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| 刊名 | ACS MEDICINAL CHEMISTRY LETTERS
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| 出版日期 | 2011-04 |
| 卷号 | 2期号:4页码:303-306 |
| 关键词 | Orphan GPR-139 agonists G-protein Coupled receptor CNS hydrazinecarboxamide |
| ISSN号 | 1948-5875 |
| DOI | 10.1021/ml100293q |
| 文献子类 | Article |
| 英文摘要 | GPR139 is an orphan G-protein coupled receptor (GPCR) Which is primarily expressed in the central nervous system (CNS). In order to explore the biological function of this receptor, selective tool compounds are required. A screening campaign identified compound 1a as a high potency PR139 agonist with an EC(50) = 39 nM in a calcium mobilization assay in CHO-K1 cells stably expressing the GPR139 receptor. In the absence of a known endogenous ligand, the maximum effect was set as 100% for 1a. Screening against 90 diverse targets revealed no cross-reactivity issues. Assessment of the pharmacokinetic properties showed limited utility,as in vivo tool compound in rat with a poor whole brain exposure of 61 ng/g and a brain/plasma (b/p) ratio of 0.03. Attempts to identify a more suitable analogue identified the des-nitrogen analogue is with a reduced polar surface area of 76.7 angstrom(2) and an improved b/p ratio of 2.8. The whole brain exposure remained low at 95 ng/g due to a low plasma exposure. |
| WOS关键词 | CENTRAL-NERVOUS-SYSTEM |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000289613200010 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278564]  |
| 专题 | 药物化学研究室 |
| 通讯作者 | Smith, Garrick |
| 作者单位 | 1.Neurosci Drug Discovery Denmark, DK-2500 Valby, Denmark; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.Lundbeck Res USA, Paramus, NJ 07652 USA |
| 推荐引用方式 GB/T 7714 | Shi, Feng,Shen, Jing Kang,Chen, Danqi,et al. Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139[J]. ACS MEDICINAL CHEMISTRY LETTERS,2011,2(4):303-306. |
| APA | Shi, Feng.,Shen, Jing Kang.,Chen, Danqi.,Fog, Karina.,Thirstrup, Kenneth.,...&Smith, Garrick.(2011).Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139.ACS MEDICINAL CHEMISTRY LETTERS,2(4),303-306. |
| MLA | Shi, Feng,et al."Discovery and SAR of a Series of Agonists at Orphan G Protein-Coupled Receptor 139".ACS MEDICINAL CHEMISTRY LETTERS 2.4(2011):303-306. |
入库方式： OAI收割
来源：上海药物研究所
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