CORE 005 – CHEMICAL SYNTHESIS AND HIGH-THROUGHPUT ANALYTICS SHARED RESOURCE PROJECT SUMMARY/ABSTRACT The Vanderbilt Chemical Synthesis and High-throughput Analytics Shared Resource (CSHTASR) provides state-of-the-art capabilities for the Vanderbilt-Ingram Cancer Center (VICC) research community, inclusive of our VICC members and partners at Meharry Medical College, Tennessee State University, and other NCI Cancer Centers. CSHTASR works to harness the power of chemistry and assay technologies to support research requiring the application or discovery of chemical tools to answer biological questions. Projects supported by this shared resource include: • Medicinal chemistry; including hit optimization and hit-to-lead activities, as well as discovery of novel compounds for pre-clinical or hypothesis-driven in vitro studies • Large-scale synthesis (10-100 grams) and compound formulation to support in vivo animal studies • Synthesis of isotopically labeled compounds including metabolites for mass spectral quantification in clinical samples • Synthesis and design of affinity and fluorescent probes • Synthesis of natural and unnatural nucleotides and peptides • High-throughput instrumentation that provides static and kinetic readouts for multiple assays including biochemical, cell-based, phenotypic, high-content image-based, 3D culture models, and whole organisms • Functional genomic screens to identify novel drug targets and mechanism(s) of drug action/resistance • Kinetic assays to support complex dynamic models • “Focused” compound/drug library screening and drug combinations – e.g., FDA drug collection (1,300), anti-cancer set (>1,000), etc., for translational projects • Full high-throughput screening campaigns of diverse, large (>350,000) compound libraries, which is coordinated with medicinal chemistry to discover new chemistry and novel compounds for disease- related targets. The CSHTASR provides these services through a combination of instrument technology and staff expertise. Institutional and NIH funds have been invested to acquire leading-edge instrumentation required for effective and efficient CSHTASR services. In addition, our compound and FGS libraries are valuable material resources that allow interrogation of biological activity, providing insight into target/pathway identification and starting points for chemical probe optimization. The CSHTASR employs a highly trained leadership and support staff with extensive experience and expertise in advanced chemistry techniques and HTS methodologies.