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.

项目摘要 检测开发和 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 中心的总体使命是为优先 AD 目标开发新型先导化合物（总体 里程碑 3)。为了实现这一目标，ADHTS 核心将执行主要和辅助分析支持 对选定目标的研究以支持化合物筛选和迭代结构活性关系 (SAR) 研究。对于先导物发现的先进目标，ADHTS 核心将有助于设计 特定的潜在客户生成策略并启用体外测试流程方案。这将包括支持的分析 具体的分子发现方法（即 HTS、基于结构的设计、片段筛选等）， 在二次分析中验证已识别的命中，以及迭代命中到先导 SAR 研究。体外测定将 包括主要和次要药理学表征，以及 ADME/Tox 替代物和 药物特性测量。在某些情况下，体外测定将得到相关的补充 计算机模型将有助于分子假设测试和物理分子的优先级排序 实验。 ADHTS核心将由HTS专家、药物研究所所长张中银博士领导 Discovery 和高通量/高内涵化学基因组学筛选设施的教职主任 普渡大学。 ADHTS 核心将由两名敬业的职员级科学家和两名博士后组成。 博士生。此外，药物发现研究所和高通量/高含量实验室的工作人员 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受到指导 由具有工业和学术分析开发以及 HTS 经验的专家顾问委员会组成。 ADHTS 核心的具体目标是： 具体目标 1：鉴定适合体外测定的指定靶点。 具体目标 2：通过 HTS 针对选定目标进行检测开发和命中发现。 具体目标 3：Hit-to-Lead 研究。