Electrophysiological characterization of a novel Kv channel blocker N,N '-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide found in virtual screening
文献类型：期刊论文
| 作者 | Gao, Zhao-bing1 ; Chen, Xue-qin1; Jiang, Hua-liang1,2; Liu, Hong1,2; Hu, Guo-yuan1
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2008-04 |
| 卷号 | 29期号:4页码:405-412 |
| 关键词 | blocker hippocampal neurons N,N '-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide patch-clamping recording virtual screening voltage-gated K(+)channel |
| ISSN号 | 1671-4083 |
| DOI | 10.1111/j.1745-7254.2008.00777.x |
| 文献子类 | Article |
| 英文摘要 | Aim: N,N'-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide (OMBSA) is a hit compound with potent voltage-gated K+ (Kv) channel-blocking activities that was found while searching the MDL Available Chemicals Directory with a virtual screening approach. In the present study, the blocking actions of OMBSA on Kv channels and relevant mechanisms were characterized. Methods: Whole-cell voltage-clamp recording was made in acutely dissociated hippocampal CA1 pyramidal neurons of newborn rats. Results: Superfusion of OMBSA reversibly inhibited both the delayed rectifier (I-K) and fast transient K+ currents (I-A) with IC50 values of 2.1 +/- 1.1 mu mol/L and 27.8 +/- 1.5 mu mol/L, respectively. The inhibition was voltage independent. OMBSA markedly accelerated the decay time course of I-K, without a significant effect on that of I-A. OMBSA did not change the activation, steady-state inactivation of I-K, and its recovery from inactivation, but the compound caused a significant hyperpolarizing shift of the voltage dependence of the steady-state inactivation of I-A and slowed down its recovery from inactivation. Intracellular dialysis of OMBSA had no effect on both I-K and I-A. Conclusion: The results demonstrate that OMBSA blocks both I-K and I-A through binding to the outer mouth of the channel pore, as predicted by the molecular docking model used in the virtual screening. In addition, the compound differentially moderates the inactivation kinetics of the K+ channels through allosteric mechanisms. |
| WOS关键词 | TRANSIENT FOREBRAIN ISCHEMIA ; CEREBELLAR GRANULE NEURONS ; OUTWARD POTASSIUM CURRENT ; CA1 PYRAMIDAL NEURONS ; PREVENTS APOPTOSIS ; K+ CHANNELS ; DISCOVERY ; CURRENTS ; ASSAY ; ENHANCEMENT |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000254559000001 |
| 出版者 | BLACKWELL PUBLISHING |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272943]  |
| 专题 | 药物化学研究室 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 药理学第二研究室 神经药理学研究国际科学家工作站 |
| 通讯作者 | Liu, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Discovery & Design, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Gao, Zhao-bing,Chen, Xue-qin,Jiang, Hua-liang,et al. Electrophysiological characterization of a novel Kv channel blocker N,N '-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide found in virtual screening[J]. ACTA PHARMACOLOGICA SINICA,2008,29(4):405-412. |
| APA | Gao, Zhao-bing,Chen, Xue-qin,Jiang, Hua-liang,Liu, Hong,&Hu, Guo-yuan.(2008).Electrophysiological characterization of a novel Kv channel blocker N,N '-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide found in virtual screening.ACTA PHARMACOLOGICA SINICA,29(4),405-412. |
| MLA | Gao, Zhao-bing,et al."Electrophysiological characterization of a novel Kv channel blocker N,N '-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl)]bis(4-methyl)-benzenesulfonamide found in virtual screening".ACTA PHARMACOLOGICA SINICA 29.4(2008):405-412. |
入库方式： OAI收割
来源：上海药物研究所
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