A HTS assay for voltage-gated ion channel targets

电压门控离子通道靶标的 HTS 测定

• 批准号: 6790321
• 负责人: Janet Kay Robertson
• 金额: $ 19.93万
• 依托单位: MEMBRANE ASSAYS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790321
• 关键词: bioassay; bioengineering /biomedical engineering; biomedical device power system; biomedical equipment development; biotechnology; cell line; computer system design /evaluation; consumable /disposable biomedical equipment; drug discovery /isolation; electrical measurement; electrical property; high throughput technology; ion transport; voltage gated channel

DESCRIPTION (provided by applicant): Membrane Assays, Inc. (MAI) seeks to develop and commercialize a high throughput screening (HTS) assay for voltage-gated ion channel targets. The assay is called the Ion Channel Assay (ICA). The ICA uses an electric field to stimulate voltage-gated ion channels. The cellular response is detected optically using fluorescence technology. The ICA is an enhanced 96-well microwell plate. On the bottom surface of each of the 96 wells are microelectrodes. Cells grown on the bottom of the well make electrical contact with the microelectrodes. When a voltage is applied between the electrodes, the local electrical potential across the cellular membrane is altered triggering a response by the voltage-gated ion channels. The action of a pharmaceutical to block, increase or decrease this response can then be measured. Voltage-gated ion channels play a critical role in such biological processes as the beating of the human heart, the contraction of muscles, and the release of hormones. Therefore, these channels are also important drug targets. No effective manner of rapidly testing the action of a pharmaceutical against a voltage-gated ion channel exists. Traditional patch clamping is too slow and even the new automated patch clamp products, currently in beta testing, do not have the throughput required. The result is missed good drugs. In addition, unknown side-effects of pharmaceuticals on a particular voltage-gated ion channel in the heart, the hERG channel, have led to the removal of 5 drugs from U.S. market. Thus, even if the target molecular of a pharmaceutical is not a voltage-gated ion channel potential new drugs must still be tested against a voltage-gated ion channel, the hERG channel, to uncover side-effects. MAI proposes to develop a critically needed HTS assay for voltage-gated ion channel targets. The assay is easy to use and compatible with equipment currently in place at most large pharmaceutical companies. Phase I funds will be used to manufacture 100, 96-well plate devices. The fabrication of these first 100 devices will verify the technical feasibility of the proposed manufacturing process and provide plates for ongoing biological testing and assay development. Electrical testing will also be performed.

描述（由申请人提供）：膜分析公司（MAI）试图开发和商业化电压门控离子通道目标的高吞吐量筛选（HTS）测定。该测定称为离子通道测定（ICA）。 ICA使用电场刺激电压门控离子通道。使用荧光技术光学检测到细胞反应。 ICA是增强的96孔微孔板。在96孔中的每个井的底部表面都是微电极。生长在井底上的细胞与微电极进行电接触。当电极之间施加电压时，跨细胞膜的局部电势会改变电压门控离子通道的响应。可以测量药物阻断，增加或减少此反应的作用。 电压门控离子通道在人心脏跳动，肌肉收缩和激素释放等生物学过程中起着关键作用。因此，这些通道也是重要的药物靶标。没有有效测试药物对电压门控离子通道的作用的有效方式。传统的补丁夹具太慢，即使是当前正在Beta测试中的新自动化贴片夹产品也没有所需的吞吐量。结果错过了好毒品。此外，在HERG频道的特定电压门控通道上，药物对药物的副作用未知，导致从美国市场中除去了5种药物。因此，即使药物的靶分子不是电压门控通道潜在的新药，仍然必须针对电压门控离子通道HERG通道进行测试，以揭示副作用。 MAI建议为电压门控离子通道靶标开发急需的HTS测定法。该测定法很容易使用，并且与当前大多数大型制药公司目前设有的设备兼容。第一阶段资金将用于制造100台96孔板设备。前100个设备的制造将验证拟议的制造过程的技术可行性，并为正在进行的生物测试和测定开发提供板。电气测试也将进行。