Open Drug Discovery Center for Alzheimer's Disease

总结 为了解决AD药物发现的预期目标类别多样性的挑战，开放式AD测定 开发和高通量筛选（HTS）核心（检测和筛选核心）已经建立了一个 创新运营结构，利用广泛的专业知识和能力进行反倾销目标定位 公共和私营部门的评估和化学探针发现。核心将由 埃默里大学的运营中心，并与世界领先的联合航空公司合作， 合作伙伴，他们将提供专门的检测、筛选和库。合作伙伴包括Baylor 医学院用高效果蝇模型，华盛顿大学用人类iPSC- 用于靶点验证的基于分析的Diamond Synchrotron，用于基于片段的筛选的 基因组学联盟（SGC）在各种检测和筛选方面拥有丰富的经验，Charles River实验室与 其HTS和药理学的多样性库，X-Chem及其独特的DNA编码库，阿尔茨海默氏症 研究英国牛津药物发现研究所的一套基于细胞的化学探针功能测定 表征，匹兹堡大学与AD动物模型的体内靶点参与和疗效 研究，以及礼来公司在AD靶点和药物开发方面的专业知识。与我们的联合互补 专业知识和能力，以及与生物信息学、结构生物学、医学化学和行政管理的综合运作 和数据核心，我们将通过创建实验试剂和 验证命中，以填充每个优先目标的目标启用包（TEP）， 评估一组不同的治疗假设。检测和筛选核心旨在（i）提供 对指定靶点进行实验验证，然后开发一级和二级检测试剂盒， 实现命中发现，（ii）对优先目标实施HTS和高内容筛选（HCS）活动， 发现经验证的命中，和（iii）开发和利用化学探针表征的功能测定。超过 该项目为期5年，完成这些目标将为多达100个提名目标提供实验证据， 推进50个目标，用于开发分析包，执行30个HTS或HCS活动，用于命中发现， 并向Open-AD提供15个目标的验证命中系列。对于每个目标，所有试剂和工具将被释放 作为TEPs的一部分 1

SUMMARY To address challenges of the anticipated diversity of target classes for AD drug discovery, the Open-AD Assay Development and High Throughput Screening (HTS) Core (Assay and Screen Core) has established an innovative operational structure that harnesses a wide range of expertise and capabilities for AD target evaluation and chemical probe discovery from both public and private sectors. The Core will be organized with an operational hub at Emory University and spokes of expanded capabilities with world-leading Associated Partners, who will contribute specialized assays, screens, and libraries. Associated Partners include Baylor College of Medicine with highly efficient Drosophila models, the University of Washington with human iPSC- based assays for target validation, the Diamond Synchrotron for fragment-based screens, the Structural Genomics Consortium (SGC) for rich experience in diverse assays and screens, Charles River Laboratories with its diversity libraries for HTS and pharmacology, X-Chem with its unique DNA-encoded libraries, Alzheimer’s Research UK Oxford Drug Discovery Institute for a suite of cell-based functional assays for chemical probe characterization, the University of Pittsburgh with AD animal models for in vivo target engagement and efficacy studies, and Eli Lilly for their expertise in AD targets and drug development. With our combined complementary expertise and capabilities and integrated operation with Bioinformatics, Structural Biology, MedChem, and Admin and Data Cores, we will support the overarching goal of Open-AD by creating experimental reagents and validated hits to populate Target Enabling Packages (TEPs) for each prioritized target in order to catalyze robust evaluation of a diverse set of therapeutic hypotheses. The Assay and Screen Core aims (i) to provide experimental validation for nominated targets followed by development of primary and secondary assays to enable hit discovery, (ii) implement HTS and high content screening (HCS) campaigns for prioritized targets to discover validated hits, and (iii) to develop and utilize functional assays for chemical probe characterization. Over the 5-year project, completion of these aims will generate experimental evidence for up to 100 nominated targets, advance 50 targets for development of assay packages, execute 30 HTS or HCS campaigns for hit discovery, and deliver validated hit series for 15 targets to Open-AD. For each target, all reagents and tools will be released as TEPs to the scientific community. 1