PROJECT SUMMARY – DRUG DISCOVERY SHARED RESOURCE (DDSR) The Ohio State University Comprehensive Cancer Center (OSUCCC) Drug Discover Shared Resource (DDSR) supports OSUCCC members to discover and develop small molecules as probes of molecular pathways implicated in tumor growth. We work with investigators to optimize the properties of chemical agents against diverse therapeutic targets to advance preclinical and clinical development. This facility was initially established in 2011 as the developing Medicinal Chemistry Shared Resource (MCSR). The MCSR became a full CCSG shared resource in 2015. In 2022, we added high throughput screening (HTS) capabilities and renamed this facility the Drug Discovery Shared Resource. The DDSR comprises two integrated cores: Medicinal Chemistry (DDSR-MC) and High-Throughput / High-Content Screening (DDSR-HTS). These cores provide crucial services for investigators seeking to identify new therapeutic candidates and tool compounds. The DDSR supports investigators conducting preclinical in vitro and in vivo studies by offering multidisciplinary expertise in medicinal chemistry, process chemistry, rational structure-based design, molecular pharmacology, and modern plate- based screening technologies. Key services provided by DDSR-MC include custom synthesis and lead optimization, including structure activity relationship analysis and structure-based optimization. Key services provided by the DDSR-HTS include access to plated libraries of over 150,000 drugs and diversity compounds that can be manipulated with automated liquid handlers. These can be analyzed for biological activity using multiple detection systems including modern high content confocal microscopy and high throughput flow cytometry. The Specific Aims of the DDSR are: 1) enable researchers to develop chemical probes of cancer biology; 2) optimize hit and lead molecules through the design and synthesis of analogs with improved drug-like properties for translational development