Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay
文献类型：期刊论文
| 作者 | Li, Qunyi2,3; Rottlander, Mario1; Xu, Mingkai2,3; Christoffersen, Claus Tornby1; Frederiksen, Kristen1; Wang, Ming-Wei2,3 ; Jensen, Henrik Sindal1
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| 刊名 | ANALYTICAL BIOCHEMISTRY
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| 出版日期 | 2011-11-01 |
| 卷号 | 418期号:1页码:66-72 |
| 关键词 | KCNQ Kv7 Patch clamp Stable cell line Thallium flux (86)Rubidium flux Potassium channel opener High-throughput screening |
| ISSN号 | 0003-2697 |
| DOI | 10.1016/j.ab.2011.06.040 |
| 文献子类 | Article |
| 英文摘要 | To develop a real-time thallium flux assay for high-throughput screening (HTS) of human KCNQ4 (Kv7.4) potassium channel openers, we used CHO-K1 cells stably expressing human KCNQ4 channel protein and a thallium-sensitive dye based on the permeability of thallium through potassium channels. The electrophysiological and pharmacological properties of the cell line expressing the KCNQ4 protein were found to be in agreement with that reported elsewhere. The EC50 values of the positive control compound (retigabine) determined by the thallium and (86)rubidium flux assays were comparable to and consistent with those documented in the literature. Signal-to-background (S/B) ratio and Z factor of the thallium influx assay system were assessed to be 8.82 and 0.63, respectively. In a large-scale screening of 98,960 synthetic and natural compounds using the thallium influx assay, 76 compounds displayed consistent KCNQ4 activation, and of these 6 compounds demonstrated EC50 values of less than 20 mu mol/L. and 2 demonstrated EC50 values of less than 1 mu mol/L. Taken together, the fluorescence-based thallium flux assay is a highly efficient, automatable, and robust tool to screen potential KCNQ4 openers. This approach may also be expanded to identify and evaluate potential modulators of other potassium channels. (C) 2011 Elsevier Inc. All rights reserved. |
| WOS关键词 | CA2+-ACTIVATED K+ CHANNELS ; HAIR-CELLS ; INNER-EAR ; ACTIVATION ; RETIGABINE ; MUTATION ; VALIDATION ; BMS-204352 ; MODULATOR ; DEAFNESS |
| 资助项目 | H. Lundbeck[00000000] ; Ministry of Science and Technology of China[2009ZX09302-001] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000294836300010 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278363]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.H Lundbeck & Co AS, Neurosci Drug Discovery, DK-2500 Copenhagen, Denmark 2.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Li, Qunyi,Rottlander, Mario,Xu, Mingkai,et al. Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay[J]. ANALYTICAL BIOCHEMISTRY,2011,418(1):66-72. |
| APA | Li, Qunyi.,Rottlander, Mario.,Xu, Mingkai.,Christoffersen, Claus Tornby.,Frederiksen, Kristen.,...&Jensen, Henrik Sindal.(2011).Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay.ANALYTICAL BIOCHEMISTRY,418(1),66-72. |
| MLA | Li, Qunyi,et al."Identification of novel KCNQ4 openers by a high-throughput fluorescence-based thallium flux assay".ANALYTICAL BIOCHEMISTRY 418.1(2011):66-72. |
入库方式： OAI收割
来源：上海药物研究所
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