AN ULTRA HIGH THROUGHPUT SYSTEM FOR DRUG DISCOVERY

用于药物发现的超高通量系统

• 批准号: 6017762
• 负责人: SARAH A SPORN
• 金额: $ 10.3万
• 依托单位: ANALYTICAL BIOLOGICAL SERVICES, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2000-06-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6017762
• 关键词: bioassay; biomedical automation; biomedical equipment development; drug discovery /isolation; luminescence; molecular film; protease inhibitor

This project aims at developing an ultra-high throughput (UHTS; >100,000 compounds / day) assay system for drug discovery. The system will utilize a new sprocket driven carrier tape. The tapes consist of 10 ul wells in a standard 384 well microtiter plate format, arrayed sequentially on a roll of polypropylene tape. These types are being developed for high Capacity easy access compound storage. We propose to use these tapes for low volume (approximately 5ul) assays. In Phase I, we will be developing protease inhibition assays, since proteases are a major therapeutic target. These assays will utilize a highly sensitive chemiluminescence detection method. In Phase I, 384 well sections of the tapes will be placed in an appropriate adapter and luminescence will be detected using a 384 well luminometer. In Phase II, additional chemiluminescence and fluorescence based assays, and instrumentation to automate the assay process will be developed. This system will meet the need in the pharmaceutical industry for UHTS systems, which require only minute amounts of valuable compound libraries. PROPOSED COMMERCIAL APPLICATIONS: Pre-clinical drug discovery is nearly a six billion dollar market. It requires the screening of many hundreds of thousands of compounds per project and limited compound collections must be used for multiple projects. The proposed ultra-high throughput system is aimed at meeting those requirements by providing a low volume assay system that will be capable of screening over 100,000 compounds per day.

该项目旨在开发用于药物发现的超高通量（UHTS; > 100，000化合物/天）测定系统。该系统将使用新的链轮驱动载带。所述带由10 μ l威尔斯孔组成，所述孔为标准384孔微量滴定板形式，顺序排列在聚丙烯带卷上。这些类型正在开发的高容量易于访问的复合存储。我们建议将这些胶带用于低容量（约5 ul）测定。在第一阶段，我们将开发蛋白酶抑制试验，因为蛋白酶是主要的治疗靶点。这些试验将采用高度灵敏的化学发光检测方法。在第I阶段，将胶带的384孔切片置于适当的适配器中，并使用384孔光度计检测发光。在第二阶段，将开发额外的基于化学发光和荧光的测定以及自动化测定过程的仪器。该系统将满足制药行业对UHTS系统的需求，该系统仅需要少量有价值的化合物库。拟议的商业应用：临床前药物发现是近60亿美元的市场。每个项目需要筛选数十万种化合物，有限的化合物集合必须用于多个项目。所提出的超高通量系统旨在通过提供每天能够筛选超过100，000种化合物的低容量测定系统来满足这些要求。