Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques

doi:10.1038/aps.2015.142

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	Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques
	Yue, Jin-feng 1; Qiao, Guan-hua 1; Liu, Ni 2,3,4; Chen, Xue-qin 1; Nan, Fa-jun2 ; Gao, Zhao-bing1
刊名	ACTA PHARMACOLOGICA SINICA
	2016-01
卷号	37 期号:1 页码:105-110
关键词	KCNQ2 channel activator high-throughput screening thallium flux assay automated patch-clamp ZG1732 ZG2083
ISSN号	1671-4083
DOI	10.1038/aps.2015.142
文献子类	Article
英文摘要	Aim: To establish an improved, high-throughput screening techniques for identifying novel KCNQ2 channel activators. Methods: KCNQ2 channels were stably expressed in CHO cells (KCNQ2 cells). Thallium flux assay was used for primary screening, and 384-well automated patch-clamp IonWorks Barracuda was used for hit validation. Two validated activators were characterized using a conventional patch-clamp recording technique. Results: From a collection of 80 000 compounds, the primary screening revealed a total of 565 compounds that potentiated the fluorescence signals in thallium flux assay by more than 150%. When the 565 hits were examined in IonWorks Barracuda, 38 compounds significantly enhanced the outward currents recorded in KCNQ2 cells, and were confirmed as KCNQ2 activators. In the conventional patch-clamp recordings, two validated activators ZG1732 and ZG2083 enhanced KCNQ2 currents with EC50 values of 1.04 +/- 0.18 mu mol/L and 1.37 +/- 0.06 mu mol/L, respectively. Conclusion: The combination of thallium flux assay and IonWorks Barracuda assay is an efficient high-throughput screening (HTS) route for discovering KCNQ2 activators.
资助项目	National Natural Science Foundation of China Grant for Excellent Key Laboratory[81123004] ; National Natural Science Foundation of China[61327014] ; National Natural Science Foundation of China[61175103] ; National Natural Science Foundation of China[91413122] ; Shanghai Municipal Science and Technology Commission[13JC1406700] ; External Cooperation Program of BIC, Chinese Academy of Sciences[1536631KYSB20130003]
WOS关键词	POTASSIUM CHANNEL ; KV7 CHANNELS ; EPILEPSY ; IDENTIFICATION ; GENE
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:5613581
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000367514700013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276269]
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药物化学研究室神经药理学研究国际科学家工作站
通讯作者	Nan, Fa-jun
作者单位	1.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China; 3.E China Normal Univ, Dept Chem, Shanghai 200062, Peoples R China; 4.E China Normal Univ, Inst Med Chem, Shanghai 200062, Peoples R China
推荐引用方式 GB/T 7714	Yue, Jin-feng,Qiao, Guan-hua,Liu, Ni,et al. Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques[J]. ACTA PHARMACOLOGICA SINICA,2016,37(1):105-110.
APA	Yue, Jin-feng,Qiao, Guan-hua,Liu, Ni,Chen, Xue-qin,Nan, Fa-jun,&Gao, Zhao-bing.(2016).Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques.ACTA PHARMACOLOGICA SINICA,37(1),105-110.
MLA	Yue, Jin-feng,et al."Novel KCNQ2 channel activators discovered using fluorescence-based and automated patch-clamp-based high-throughput screening techniques".ACTA PHARMACOLOGICA SINICA 37.1(2016):105-110.