Assay Development and High Throughput Screening Core

项目总结分析开发和HTS核心 Assay Development&HTS(ADHTS)核心将与其他技术核心协同工作以实现 ADDD中心的总体任务是为优先AD目标开发新的先导化合物(总体 里程碑3)。为此，ADHTS Core将执行一次和二次化验启用 支持化合物筛选和迭代构效关系(SAR)的目标选择研究 学习。对于先进的铅发现目标，ADHTS核心将有助于设计 特定的铅生成策略，并启用体外测试流程方案。这将包括支持的化验 特定的分子发现方法(即HTS、基于结构的设计、片段筛选等)， 在二次分析中确认确认的命中，以及迭代的命中到领先的SAR研究。体外检测将会 包括初级和次级药理学表征，以及ADME/TOX代用品和 药物性测量。在某些情况下，体外试验将得到相关研究的支持。 将有助于分子假设检验和物理分子优先排序的Silico模型 实验。 ADHTS核心将由HTS专家、药物研究所所长张忠印博士领导 发现号和高通量/高含量化学基因组筛选设施的教研室主任 普渡大学。ADHTS核心将由两名专职工作人员级别的科学家和两名员额组成。 博士生。此外，药物发现研究所内的工作人员和高通量/高含量 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 由在工业和学术分析开发和HTS方面经验丰富的专家组成的顾问委员会提供。 ADHTS核心的具体目标是： 具体目标1：鉴定体外可进行分析的提名靶标。 具体目标2：通过HTS对选定的目标进行分析开发和HIT发现。 具体目标3：命中到领先研究。

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.