Drug Development Core Shared Resource

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PROJECT SUMMARY / ABSTRACT The mission of the Drug Development Core (DDC) is to make state-of-the-art drug development accessible and affordable to UWCCC members. Development of innovative therapies is a priority area of research in the UWCCC Strategic Plan, and drug development requires specialized expertise in synthetic, computational, and analytical chemistry. The overarching scientific discipline in the DDC is medicinal chemistry in its broadest sense. DDC offers compound discovery by high throughput screening (HTS); computational chemistry for in silico virtual screening and modeling; chemical informatics to identify and prioritize compounds; chemical synthesis of potent, selective, and pharmacologically viable compounds; and analytical chemistry to support UWCCC clinical trials with pharmacokinetic (PK) and pharmacodynamic (PD) assays. Aim 1 is to advance UWCCC member drug development research by providing broad medicinal chemistry expertise and infrastructure encompassing discovery, synthetic chemistry, computational chemistry, analytical chemistry, and pharmacology of chemoprevention and anticancer agents. DDC staff advise UWCCC members in all aspects of experimental design and data interpretation. The highly-skilled and experienced staff are experts in the use of state-of-the-art equipment for microwave-facilitated organic synthesis, analytical and preparative HPLC, mass spectrometry, combi-flash chromatography, tip-less and tip-based liquid handling robotics, assay quantification in 96 through 1536-well plate readers, and high throughput computing. Aim 2 is to support clinical trials conducted at UWCCC by providing analytical chemistry expertise needed to evaluate the pharmacokinetic and pharmacodynamic properties of study drugs and to provide patient sample storage with robust and secure database documentation of all samples. DDC staff are tightly coordinated with the clinical trial enterprise at UWCCC including participation in the Cancer Therapy Discovery and Development (CTD2) group and the Disease Oriented Teams to support UWCCC members with assays for drug concentrations and biomarkers on any clinical substrate and storage of study samples from clinical trials. In the current funding period, the core provided support for 394 UWCCC studies. Aim 3 is to train UWCCC members, their staff, and students in drug development processes and the productive application of state-of-the-art, well-maintained equipment to their specific research goals and provide 24/7 access to this drug development focused infrastructure. Impact on UWCCC: The DDC has supported the research of 128 unique UWCCC members during the current funding cycle and is well-staffed and equipped to meet the future drug development needs of UWCCC members. Continued support from the CCSG will enable highly experienced DDC staff scientists to invest time and expertise in consulting with UWCCC members on future projects and on advancing current promising molecules along the development pathway to the clinic.