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.
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