PROJECT SUMMARY / ABSTRACT The Drug Development Core (DDC) directly supports the UWCCC mission to develop innovative therapies by providing cost-effective, cutting-edge, high-throughput screening (HTS) services; medicinal chemistry and lead optimization services; and pharmacokinetic (PK) and pharmacodynamic (PD) services to support clinical trials. These services are supported by extensive expertise, state-of-the-art equipment, and cutting-edge computational tools for assay design, synthetic chemistry, computational chemistry, analytical chemistry, and pharmacology. Through a mission-centered set of specific aims, the DDC will achieve a high level of support for UWCCC members. Specific Aim 1: Advance UWCCC member drug development research by providing expertise and resources for compound discovery, medicinal chemistry, computational chemistry, and pharmacology of chemoprevention and anticancer agents. The primary goal of Specific Aim 1 is to provide the expertise, equipment, and computational tools required to fully enable UWCCC users. Specifically, the DDC staff will advise on experimental design, data acquisition, and data analysis to ensure rigor and reproducibility of high impact drug development research in a cost-effective manner. Impact: 13 HTS campaigns, 10 patents, and 10 drug leads. Specific Aim 2: Support clinical trials conducted at UWCCC by providing the expertise and infrastructure needed to evaluate the pharmacokinetic and pharmacodynamic properties of study drugs. To achieve this aim, the DDC will provide patient sample storage with a robust and secure database system to document all samples. Additionally, the DDC will provide analytical expertise to properly sample, analyze, and quantify drugs and drug metabolites from patient tissues. These services are critical to UWCCC participation in NCI sponsored UM1 programs, NCI’s National Clinical Trials Network (NCTN), and industry sponsored clinical trials. In the current funding period, the DDC provided support for 394 UWCCC studies including 209 NCI sponsored studies. Given the proposed expansion of clinical trials by the Developmental Therapeutics program, we predict this number to increase in the next funding period. Specific Aim 3: Train UWCCC members, their staff, and students in drug development processes and the productive use of state-of-the-art equipment to meet their research goals. The highly experienced DDC staff will ensure that equipment is well maintained, highly reliable, and available for UWCCC members, their staff, and students on a 24/7 basis. Additionally, the DDC staff will routinely present studies and new technologies to PI’s, postdocs, and trainees. The DDC has trained over 168 users associated with the UWCCC during the current funding period. Through these Specific Aims, DDC will not only support the mission of the UWCCC but also provide direct support to UWCCC members to maximize their impact and further advance cutting-edge cancer research. DDC supported 109...