A High-Throughput Cell-based Drug Discovery System

高通量细胞药物发现系统

• 批准号: 6885328
• 负责人: Rajan Kumar
• 金额: $ 64.4万
• 依托单位: GENOME DATA SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885328
• 关键词: apoptosis; bioengineering /biomedical engineering; biomedical automation; biomedical equipment development; biotechnology; cell mediated lymphocytolysis test; chemical registry /resource; computer program /software; drug discovery /isolation; drug screening /evaluation; gene expression profiling; high throughput technology; method development; microarray technology; miniature biomedical equipment; pharmacokinetics

DESCRIPTION (provided by applicant): This Phase II SBIR project is focused at the development of a high-throughput screening method and instrument for drug discovery using miniaturized, cell-based assays. For developing new drugs against complex diseases such as diabetes, cancer and neurological and cardiovascular disorders, high throughput screening using cell-based assays will be essential. Miniaturization of cell-based assays for automation and reduced costs is required. GeneCard-HTS enables drug discovery using adherent cell-based assays. During the Phase I project, the feasibility of the GeneCard approach was demonstrated using apoptosis assays. A prototype instrument to automate GeneCard assay process was developed and assembled. During Phase II, the versatility and flexibility of the GeneCard platform will be investigated by performing other cell-based assays used in drug discovery. The proposed plan investigates the following three specific aims: 1. Build a high-throughput screening prototype system based on GeneCard technology (GeneCard-HTS). 2. Miniaturize multiple cell-based assays for GeneCard-HTS platform. We will miniaturize four commonly used drug discovery assays in the GeneCard-HTS platform, i) Apoptosis assays using the Mitosensor reagents, ii) cell-based kinase assays, iii) fluorescent cytotoxicity assays, and iv) gene expression profiling assays. We will measure the performance of these assays in GeneCard-HTS platform and compare with performance obtained at present. 3. Validate GeneCard-HTS by cell-based screening of compound libraries. In order to validate the Genecard-HTS system, we will perform screening of a 5,000 compound focused library using cell-based kinase and apoptosis assays. We will measure validation parameters such as system lifetime, operating temperature and humidity range, inter- and intra- assay variability, and day-to-day variability. Commercial applications of the proposed system include pharmaceutical and biotechnoiogy drug discovery. Further integration of the instrument based on design specifications prepared in Phase I will be performed. Screening of drug compound libraries to identify potential lead compounds will be performed.

描述（由申请人提供）：此II期SBIR项目的重点是开发使用基于细胞的小细胞测定法的高通量筛查方法和用于药物发现的仪器。对于针对糖尿病，癌症和神经系统和心血管疾病等复杂疾病的新药，使用基于细胞的测定的高吞吐量筛查至关重要。基于细胞的自动化和降低成本的小型化。 Genecard-HTS可以使用基于细胞的测定方法来发现药物。在I阶段项目中，使用凋亡测定法证明了Genecard方法的可行性。开发并组装了一种自动化Genecard分析过程的原型仪器。在II阶段期间，将通过执行用于药物发现中的其他基于细胞的测定法来研究Genecard平台的多功能性和灵活性。拟议的计划调查了以下三个具体目标： 1。建立基于GeneCard技术（Genecard-HTS）的高通量筛选原型系统。 2。对Genecard-HTS平台的多个基于细胞的测定。我们将在Genecard-HTS平台中的四个常用药物发现测定法，i）使用Mitosensor试剂的凋亡测定，ii）基于细胞的激酶测定，iii）荧光细胞毒性测定和IV）基因表达分析分析测定法。我们将在Genecard-HTS平台中衡量这些测定的性能，并与目前获得的性能进行比较。 3。通过基于细胞的化合物库来验证Genecard-HT。为了验证Genecard-HTS系统，我们将使用基于细胞的激酶和凋亡测定法对5,000个复合库进行筛选。我们将衡量验证参数，例如系统寿命，工作温度和湿度范围，间和内分析变异性以及日常变异性。 拟议系统的商业应用包括药物和生物技术学药物发现。将根据第I期准备的设计规范进一步整合仪器。将进行药物化合物文库筛选以鉴定潜在的铅化合物。