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作为用于人乙醚 - 去极化相关基因(hERG)钾通道成像的荧光探针的阿司咪唑衍生物。

Astemizole Derivatives as Fluorescent Probes for hERG Potassium Channel Imaging.

作者信息

Wang Beilei, Liu Zhenzhen, Ma Zhao, Li Minyong, Du Lupei

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University , Jinan, Shandong 250012, China.

出版信息

ACS Med Chem Lett. 2016 Jan 20;7(3):245-9. doi: 10.1021/acsmedchemlett.5b00360. eCollection 2016 Mar 10.

DOI:10.1021/acsmedchemlett.5b00360
PMID:26985309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4789673/
Abstract

The detection and imaging of hERG potassium channels in living cells can provide useful information for hERG-correlation studies. Herein, three small-molecule fluorescent probes, based on the potent hERG channel inhibitor astemizole, for the imaging of hERG channels in hERG-transfected HEK293 cells (hERG-HEK293) and human colorectal cancer cells (HT-29), are described. These probes are expected to be applied in the physiological and pathological studies of hERG channels.

摘要

活细胞中hERG钾通道的检测与成像可为hERG相关性研究提供有用信息。本文描述了三种基于强效hERG通道抑制剂阿司咪唑的小分子荧光探针,用于在转染hERG的HEK293细胞(hERG-HEK293)和人结肠癌细胞(HT-29)中对hERG通道进行成像。这些探针有望应用于hERG通道的生理和病理研究。

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Astemizole Derivatives as Fluorescent Probes for hERG Potassium Channel Imaging.作为用于人乙醚 - 去极化相关基因(hERG)钾通道成像的荧光探针的阿司咪唑衍生物。
ACS Med Chem Lett. 2016 Jan 20;7(3):245-9. doi: 10.1021/acsmedchemlett.5b00360. eCollection 2016 Mar 10.
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NBD-Based Environment-Sensitive Fluorescent Probes for the Human Ether-a-Go-Go-Related Gene Potassium Channel.用于人类醚-去极化相关基因钾通道的基于NBD的环境敏感型荧光探针
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Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole.抗组胺药阿司咪唑及其代谢产物去甲基阿司咪唑和诺阿司咪唑对HERG钾通道的阻断作用。
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Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels.在表达HERG钾通道的HEK293细胞中对[3H]阿司咪唑结合试验的验证。
J Pharmacol Sci. 2004 Jul;95(3):311-9. doi: 10.1254/jphs.fpe0040101.
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引用本文的文献

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NBD-Based Environment-Sensitive Fluorescent Probes for the Human Ether-a-Go-Go-Related Gene Potassium Channel.用于人类醚-去极化相关基因钾通道的基于NBD的环境敏感型荧光探针
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3
Aggregation-Induced Emission: Lighting Up hERG Potassium Channel.聚集诱导发光:点亮hERG钾通道
Front Chem. 2019 Feb 8;7:54. doi: 10.3389/fchem.2019.00054. eCollection 2019.
4
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Chem Cent J. 2016 Apr 30;10:24. doi: 10.1186/s13065-016-0169-9. eCollection 2016.

本文引用的文献

1
Novel intramolecular photoinduced electron transfer-based probe for the Human Ether-a-go-go-Related Gene (hERG) potassium channel.用于人类醚-去极化相关基因(hERG)钾通道的基于分子内光诱导电子转移的新型探针。
Analyst. 2015 Dec 21;140(24):8101-8. doi: 10.1039/c5an01974e.
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Fluorogenic probe for the human Ether-a-Go-Go-Related Gene potassium channel imaging.
Anal Chem. 2015 Mar 3;87(5):2550-4. doi: 10.1021/ac504763b. Epub 2015 Feb 12.
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Experimentally validated HERG pharmacophore models as cardiotoxicity prediction tools.经实验验证的 HERG 药效团模型可作为心脏毒性预测工具。
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Dynamics of hERG closure allow novel insights into hERG blocking by small molecules.hERG通道关闭的动力学为小分子阻断hERG通道提供了新的见解。
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Chimeric hERG channels containing a tetramerization domain are functional and stable.含有四聚化结构域的嵌合 hERG 通道是有功能和稳定的。
Biochemistry. 2013 Dec 23;52(51):9237-45. doi: 10.1021/bi401100a. Epub 2013 Dec 10.
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Small-molecule-based protein-labeling technology in live cell studies: probe-design concepts and applications.活细胞研究中的基于小分子的蛋白质标记技术:探针设计概念和应用。
Acc Chem Res. 2014 Jan 21;47(1):247-56. doi: 10.1021/ar400135f. Epub 2013 Aug 8.
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hERG channel function: beyond long QT.hERG 通道功能:超越长 QT 间期。
Acta Pharmacol Sin. 2013 Mar;34(3):329-35. doi: 10.1038/aps.2013.6.
8
Current pharmacogenomic studies on hERG potassium channels.当前 hERG 钾通道的药物基因组学研究。
Trends Mol Med. 2013 Apr;19(4):227-38. doi: 10.1016/j.molmed.2012.12.006. Epub 2013 Jan 29.
9
An automated docking protocol for hERG channel blockers.一种用于 hERG 通道阻滞剂的自动对接方案。
J Chem Inf Model. 2013 Jan 28;53(1):159-75. doi: 10.1021/ci300326d. Epub 2013 Jan 9.
10
Combinatorial strategies in fluorescent probe development.荧光探针开发中的组合策略。
Chem Rev. 2012 Aug 8;112(8):4391-420. doi: 10.1021/cr200355j. Epub 2012 May 23.