SMALL MOLECULE DRUG DEVELOPMENT (SMDD) SHARED RESOURCE PROJECT SUMMARY/ABSTRACT The Small Molecule Drug Development (SMDD) SR's mission is to assist researchers in creating high-quality chemical probes to test therapeutic concepts. Utilizing High-Throughput Screening (HTS) and High Content Analyses (HCA), it identifies active small molecules, aiding in the refinement of these “hits” into defined probes. The SMDD SR offers resources for drug repurposing and new small molecule discovery. From 2018-2023, the SR collaborated with 71 investigators, 58% being Case CCC members, completing 74 high-throughput screen projects and numerous custom assays. It has aided over 100 grant applications, securing over $11 million in funding. The SR has supported 100+ users from Case Western Reserve University (CWRU), University Hospitals, Cleveland Clinic, and other institutions, receiving highly positive feedback. The Specific Aims of the Small Molecule Drug Development Shared Resource are to: 1. Provide assay development and high-throughput screening services, using innovative approaches to screen bioactive compounds and diverse screening libraries. 2. Share expertise to design and optimize robust high-throughput assays tailored to specific projects. 3. Train new users, including PIs, research scientists, and trainees, in the proper and safe operation of the SR's automation equipment and manage their participation during assay development and execution. 4. Offer advice and guidance to advance hits to leads using cheminformatics and medicinal chemistry. 5. Guide users toward SRs and potential collaborating investigators in Case CCC research programs with complementary capabilities relevant to drug development. The SMDD SR's development has led to its integration with the CWRU School of Medicine (SOM) Chemical Biology Program. The SR has enhanced its microscopy capabilities with the Agilent Cytation5 HTS imager and broadened its small-molecule libraries with NCI