Small Molecule Drug Development Shared Resource

小分子药物开发共享资源 项目摘要/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，使小分子筛查和 小分子探针的鉴定。药物开发SR的使命是使调查人员能够 在384孔格式中优化可靠的分析，并在大型化学资料库中筛选这些分析以确定 新的小分子可能是创新癌症疗法的起点。在第一年，广泛的 来自凯斯西部储备大学(CWRU)、克利夫兰大学医院(UH)的调查人员 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名调查人员合作，约65% 谁是案例CCC成员，占总使用量的79%，代表7个案例CCC中的4个 程序。小分子药物开发共享资源的具体目标是： 1.提供化验开发和高通量筛查服务，使用高通量和高通量 筛选已知生物活性化合物(生物活性)文库的内容方法和多样化筛选 图书馆。 2.分享专业知识，通过以下方式设计和优化针对特定项目量身定做的强健高通量分析 PI、总监和总经理之间的协商，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，了解SR的正确和安全操作 以合理的价格提供自动化设备，并欢迎/包括他们参与化验 开发和执行。 4.提供建议和指导，通过使用化学信息学和药物化学，促进线索的命中 提供建议的战略，以确定命中的优先顺序，并将调查人员与药物化学家联系起来。 5.引导用户在Case CCC项目中使用SRS和潜在的合作调查人员 随着项目的发展，与药物开发有关的补充能力，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次或更多完全高通量筛查 以及6个或更多的试点屏幕，为未来的大规模屏幕保持强大的分析管道。另外， 该设施将扩大其设备集，以提供几个关键仪器的冗余，并将扩大其 筛选100,000个小分子文库，以匹配其他学术机构进行的典型屏幕尺寸 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.