Small Molecule Drug Development Shared Resource

小分子药物开发共享资源 项目总结/摘要 小分子药物开发共享资源（Drug Development SR）成立于 2015年9月，以解决缺乏关键基础设施的问题，使小分子筛选和 鉴定小分子探针。药物开发SR的使命是使研究者能够 优化384孔格式中的稳健测定，并在大型化学文库中筛选这些测定， 新的小分子可能是创新癌症治疗的起点。在第一年，一个广泛的 来自凯斯西储大学（CWRU）、大学医院（UH）、克利夫兰的一系列研究人员 来自杜克大学的合作者Clinic（CC）和克利夫兰的一家生物技术初创公司利用了这种药物 开发SR，证明了对小分子筛选的巨大需求。 自成立以来，药物开发SR已与17名研究者合作，约占总人数的65%。 2010年，中国移动用户使用的移动电话数量为79%，占7个移动电话用户中的4个 程序.小分子药物开发共享资源的具体目标是： 1.提供检测开发和高通量筛选服务，同时使用高通量和高通量技术， 筛选已知生物活性化合物（生物活性物质）文库的内容方法和多种筛选 图书馆. 2.分享专业知识，设计和优化针对特定项目量身定制的强大高通量检测， PI、总监和常务董事之间的磋商，以告知项目设计、执行 和故障排除。 3.培训新用户，包括PI、研究科学家和受训人员，以正确和安全地操作SR 自动化设备，并欢迎/包括他们在分析过程中的参与 开发和执行。 4.提供建议和指导，利用化学信息学和药物化学， 提供推荐的优先命中策略，并将调查人员与药物化学家联系起来。 5.在案例CCC项目中，引导用户了解SR和潜在合作研究者， 随着项目的发展，与药物开发相关的补充能力，包括与 在蛋白质组学、体外和体内药理学以及体内测试方面具有专业知识的研究人员。 展望未来，药物开发SR的目标是每年完成3个或更多的完整高通量筛选 以及6个或更多个中试筛选，以维持用于未来大规模筛选的稳健测定的管道。此外，本发明还 该设施将扩大其设备组，以在几个关键仪器中提供冗余，并将扩大其 筛选文库到100，000个小分子，以匹配其他学术研究中进行的典型筛选尺寸。 筛查中心。

SMALL MOLECULE DRUG DEVELOPMENT SHARED RESOURCES PROJECT SUMMARY/ABSTRACT The Small Molecule Drug Development Shared Resource (Drug Development SR) was established in September 2015 to address the lack of critical infrastructure enabling small molecule screening and the identification of small-molecule probes. The mission of the Drug Development SR is to enable investigators to optimize robust assays in 384-well format and to screen these assays across large chemical libraries to identify new small molecules that may be the starting point for innovative cancer therapeutics. In the first year, a wide range of investigators from Case Western Reserve University (CWRU), University Hospitals (UH), Cleveland Clinic (CC), a collaborator from Duke University, and a Cleveland biotech startup utilized the Drug Development SR, testifying to the large demand for small-molecule screening. Since its establishment, the Drug Development SR has worked with 17 investigators, approximately 65% of whom are Case CCC members, accounting for 79% of total usage, and representing 4 of the 7 Case CCC Programs. The Specific Aims of the Small Molecule Drug Development Shared Resource are to: 1. Provide assay development and high-throughput screening services, using both high-throughput and high- content approaches to screen libraries of known bioactive compounds (bioactives) and diverse screening libraries. 2. Share expertise to design and optimize robust high-throughput assays tailored to specific projects, by consultation between the PI, the Director, and the Managing Director to inform project design, execution, and troubleshooting. 3. Train new users, including PIs, research scientists, and trainees, in proper and safe operation of the SR's automation equipment at reasonable cost, and welcome/include their participation during assay development and execution. 4. Offer advice and guidance to advance hits to leads using cheminformatics and medicinal chemistry, by providing recommended strategies for prioritizing hits, and linking investigators with medicinal chemists. 5. Guide users toward SRs and potential collaborating investigators in Case CCC Programs with complementary capabilities relevant to drug development as projects evolve, including connections to researchers with expertise in proteomics, in vitro and in vivo pharmacology, and in vivo testing. Moving forward, the Drug Development SR aims to complete 3 or more full high-throughput screens per year and 6 or more pilot screens to maintain a pipeline of robust assays for future large-scale screens. Additionally, the facility will expand its equipment set to provide redundancy in several key instruments, and will expand its screening libraries to 100,000 small molecules to match typical screen sizes performed in other academic screening centers.