Assay Development and High Throughput Screening Core

检测开发和高通量筛选核心

• 批准号: 10684144
• 负责人: Zhong-Yin Zhang
• 金额: $ 85.81万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10684144
• 关键词: ABCB1 gene; Alzheimer' s Disease; Bioinformatics; Biological Assay; Chemicals; Computational Biology; Computing Methodologies; Cytochrome P450; Dedications; Dose; Ensure; Faculty; Generations; Genomics; Goals; HepG2; In Vitro; Industrialization; Lead; Libraries; Literature; Measures; Microsomes; Mission; Modeling; Molecular; Office of Administrative Management; Pattern; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Postdoctoral Fellow; Property; Recommendation; Reproducibility; Scheme; Scientist; Structure; Structure-Activity Relationship; Testing; Toxicology; Triage; Universities; Validation; Work; Yin; assay development; cytotoxicity; data management; design; doctoral student; drug discovery; experience; high throughput screening; in silico; in vitro Assay; in vitro testing; lead optimization; novel lead compound; screening; virtual screening

PROJECT SUMMARY Assay Development & HTS Core The Assay Development & HTS (ADHTS) Core will work in tandem with the other Technical Cores to achieve the overall ADDD CENTER mission of developing novel lead compounds for prioritized AD targets (Overall MILESTONE 3). To accomplish this, the ADHTS Core will perform primary and secondary assay enablement studies on selected targets to support compound screening and iterative structure activity relationship (SAR) studies. For targets that are advanced for lead discovery, the ADHTS Core will contribute to the design of a specific lead generation strategy and enable the in vitro testing flow scheme. This will include assays to support the specific molecular discovery approach (i.e. HTS, structure based design, fragment screening, etc.,), validation of identified hits in secondary assays, and iterative hit-to-lead SAR studies. The in vitro assays will include primary and secondary pharmacology characterization, as well as ADME/Tox surrogates and pharmaceutical properties measures. The in vitro assays will be complimented, in some cases, by related in silico models that will aid in molecular hypothesis testing and prioritization of molecules for physical experimentation. The ADHTS Core will be led by Dr. Zhong-Yin Zhang, an expert in HTS, the Director of the Institute for Drug Discovery and the faculty director of the high-throughput/high-content chemical genomics screening facility at Purdue University. The ADHTS core will be comprised of two dedicated staff-level scientists and two post- doctoral students. Additionally, staff within the Institute for Drug Discovery and the high-throughput/high-content chemical genomics screening facility will assist in Core activities. Importantly, Dr. Zhang and staff will be guided by an advisory board of experts with experience in industrial and academic assay development and HTS. The Specific Aims of the ADHTS Core are: Specific Aim 1: Identification of in vitro assay-amenable nominated targets. Specific Aim 2: Assay development and hit discovery via HTS for selected targets. Specific Aim 3: Hit-to-Lead studies.

项目概要分析开发和HTS核心 检测开发和HTS（ADHTS）核心将与其他技术核心协同工作，以实现 ADDD中心的总体使命是开发用于优先AD目标的新型先导化合物（总体 里程碑3）。为了实现这一点，ADHTS核心将执行主要和次要分析启用 对选定靶标进行研究，以支持化合物筛选和迭代构效关系（SAR） 问题研究对于领先发现的先进目标，ADHTS核心将有助于设计一个 特定的潜在客户开发策略，并启用体外测试流程方案。这将包括用于支持 特定分子发现方法（即HTS、基于结构的设计、片段筛选等）， 验证二次检测中识别的命中，以及迭代命中-电极导线SAR研究。体外试验将 包括主要和次要药理学表征，以及ADME/Tox替代物， 药物性能的措施。在某些情况下，体外试验将通过相关的 计算机模型，这将有助于分子假设检验和分子的优先级， 实验 ADHTS核心将由HTS专家、药物研究所所长张中银博士领导。 发现和高通量/高内容化学基因组学筛选设施的主任， 普渡大学。ADHTS核心将由两名专职科学家和两名博士后组成。 博士生。此外，药物发现研究所的工作人员和高通量/高内容 化学基因组学筛选设施将协助核心活动。重要的是，张博士和工作人员将被引导 由在工业和学术分析开发和HTS方面具有丰富经验的专家组成的咨询委员会进行。 ADHTS核心的具体目标是： 具体目标1：鉴定体外试验适用的指定靶标。 具体目标2：通过HTS针对选定靶标开发检测试剂盒并发现命中。 具体目标3：命中到铅研究。