PROJECT SUMMARY/ABSTRACT (STRUCTURE AND DRUG SCREENING SHARED RESOURCE) The Structure and Drug Screening Shared Resource (SDS-SR) provides services encompassing the key elements of early-stage drug development through lead optimization. SDS-SR is a collaboration of Structural Biology (SB), High-Throughput Screening (HTS), and Medicinal Chemistry (MC). SB, HTS, and MC frequently coordinate services for Rogel Cancer Center (Rogel) members to increase the efficiency and impact of cancer- related projects. SDS-SR enables Rogel members to use advanced structure-based drug design and/or nonbiased HTS strategies to identify chemical matter that can be advanced through a milestone-driven research plan resulting in efficient and effective discovery and development of precision oncology medicines - a strategic goal of the Rogel Cancer Center. The overall goals of SDS-SR are to identify novel molecular targets for new cancer therapeutics and to identify novel chemical leads and/or tool molecules that interact with these targets. Our services start with refining the protein target via high throughput cloning and expression through confirmation and optimization of hit binding via X-ray crystallography. Once the target is refined, it is purified in quantities ranging from micrograms to grams for high-throughput screening (HTS) assay development and large scale HTS for hit identification. Additional biophysical orthogonal assays are offered to determine whether the compound binds directly to the target prior to structure determination. Rogel members are provided with training, advisement, consultation, and specialized equipment through every step of the process. SDS-SR services are provided by scientific staff with a breadth of expertise and backgrounds in both academia and industry. Many of these services are not available through vendors or other institutions. SDS-SR continues to be an invaluable resource to Rogel members. The SDS-SR’s cohesive activities, services, and processes ensure that projects are advanced along the translational pipeline, from basic science discoveries into early cancer drug discovery.