Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds
| Autor: | Rick Phimmachack, Khachonesine Sithiphong, Andrea Ghetti, Steve Saya, George Walker, Zoya Zozulya, Antonio Guia, Jia Xu, Joseph Ligutti, Florence Chan, Mingxian Huang, Charles Sie, Huimin Tao, Tao Guoliang, Julian Yuan, David Santa Ana, Lei Wu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Patch-Clamp Techniques
Computer science Voltage clamp hERG Drug Evaluation Preclinical Amiodarone Torsades de pointes Computational biology CHO Cells Pharmacology Cricetinae Drug Discovery medicine Potassium Channel Blockers Animals Humans Patch clamp Cation Transport Proteins biology Dose-Response Relationship Drug Drug discovery Potassium channel blocker medicine.disease Potassium channel Ether-A-Go-Go Potassium Channels Electrophysiology Potassium Channels Voltage-Gated biology.protein Molecular Medicine medicine.drug |
| Zdroj: | Assay and drug development technologies. 2(5) |
| ISSN: | 1540-658X |
| Popis: | Unintended inhibition of the cardiac potassium channel human ether-a-go-go-related gene (hERG) is considered the main culprit in drug-induced arrhythmias known as torsades de pointes. Electrophysiology is the most reliable in vitro screening method for identifying potential cardiac hERG liabilities, but only the recent advent of planar electrode-based voltage clamp electrophysiology promises sufficient throughput to support the drug testing needs of most drug discovery programs. We have assessed the reliability of this new format of the voltage clamp technology in measuring the activity of small molecules on the hERG channel. Based on the results herein of a screening against a panel of well-characterized hERG-active and -inactive molecules, we demonstrate that planar electrode electrophysiology, utilizing the Sealchip and PatchXpress technology platform (AVIVA Biosciences Corp., San Diego, CA), is comparable to traditional electrophysiology based on glass micropipettes in its reliability and data content. The new technology will allow significantly higher throughput and more thorough testing of pharmaceutical compounds. |
| Databáze: | OpenAIRE |
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