The Vanderbilt Specialized Chemistry Center for Accelerated Probe Development

我们建议建立一个专门的化学中心，即加速探针开发的范德比尔特专门化学中心，以加快发现和开发高质量的探针化合物，这将对MLPCN研究网络的目标产生重大影响。基于Lindsley技术支持合成（TES）实验室和Conn实验室的基础设施，资源和广泛的药物发现（从概念到临床的击中到导致证明）经验，我们准备与MLPCN网络中的外部专业筛选和综合中心合作支持探针开发项目。由于我们的高通量药物化学技术平台和我们的M.S.和博士我们建议的中心将能够支持五（5）个探针开发项目，与内部或外部中心并行（约20个探针开发项目/年），并需要不到三个月的时间来开发探针和先进的分子工具，用于体外和/或体内概念验证实验。拟议的范德比尔特加速探针开发专业化学中心与其他中心不同，因为PI在制药行业拥有8年的从点击到引线到概念验证的经验，并在范德比尔特内按照行业标准建立了一个设备齐全的高通量合成和纯化实验室，这使得最少的人力资源能够快速开发探针化合物。我们的最初目标是提供满足或超过MPLCN指南和/或满足启动筛选的研究者的探针的特定要求的探针化合物。当与NIH/NIMH和MLPCN目标保持一致时，我们将使用部分MLPCN和Lindsley和Conn实验室的内部资源（合成/药物化学，药理学，DMPK和放射化学）在中心-推动研究项目，进一步完善和开发治疗相关靶点的探针，以确保可以进行体内概念验证实验，以提供“快速杀灭”或验证靶点作为潜在治疗剂未满足的医疗需求。最后，我们将为MLPCN内的其他化学家提供培训休假，以学习并行合成技术和库设计策略。

We are proposing the establishment of a specialized chemistry center, the Vanderbilt Specialized Chemistry Center for Accelerated Probe Development, to expedite the discovery and development of high quality probe compounds which will significantly impact the goals of the MLPCN Research Network. Building on the infrastructure, resources and broad drug discovery (hit-to-lead-to-proof of concept-to-clinic) experience within the Lindsley Technology Enabled Synthesis (TES) Lab and the Conn Lab, we are poised to support probe development projects in collaboration with external Specialty Screening and Comprehensive Centers in the MLPCN Network. Due to our state-of-the-art technology platform for high-throughput medicinal chemistry and our M.S. and Ph.D. level staff chemists, our proposed center will be capable of supporting five (5) probe development projects, with internal or external centers, in parallel (~20 probe development programs/year) and require less than three months to develop probes and advanced molecular tools for in vitro and/or in vivo proof of concept experiments. The proposed Vanderbilt Specialized Chemistry Center for Accelerated Probe Development is unique from other centers in that the PI has eight years hit-to-lead-to-proof of concept experience in the pharmaceutical industry and has built a fully equipped high-throughput synthesis and purification lab, at the industry standard, within Vanderbilt which allows minimal human resources to develop probe compounds with expedited timelines. Our initial goal will be to deliver probe compounds that meet or exceed MPLCN guidelines and/or meet specific requirements for a probe of the investigator that initiated the screen. When aligned with NIH/NIMH and MLPCN goals, we will use a portion of our MLPCN and internal resources in the Lindsley and Conn Labs (synthesis/medicinal chemistry, pharmacology, DMPK and adiochemistry) in Center-Driven Research Projects to further refine and develop probes for therapeutically relevant targets to ensure in vivo proof of concept experiments can be performed to provide 'quick kills' or validate targets as potential therapeutic agents for unmet medical needs. Finally, we will offer training sabbaticals to other chemists within the MLPCN to learn parallel synthesis techniques and library design strategies.