PROJECT SUMMARY This application is for a shared isothermal titration microcalorimeter (ITC) facility. ITC technique enables the accurate determination of ligand receptor dissociation constants and complete thermodynamic parameters, which will strengthen the research projects of a group of very productive NIH-supported faculty members in medicinal chemistry, pharmacology & toxicology, chemistry & biochemistry, molecular biology, and biophysics at the University of Arizona (UA). These investigators are funded by NIH to study the design and synthesis of small molecules for novel therapeutic targets, to develop small-molecule probes to perturb biological processes associated with various diseases, or to investigate intermolecular interactions driving biological processes. Their research addresses a wide variety of unmet medical needs, including microbial infections, neurological disorders, diabetes, and cancer. Currently, there is no ITC at the University of Arizona with low sample volume and automated sample handling capabilities. The requested instrument will have a significant impact on a large group of NIH-supported major and new users, particularly for hit validation from high throughput screening and medicinal chemistry campaigns. Further, we are confident that the new ITC will stimulate new collaborations among investigators at UA. The Arizona Center for Drug Discovery (ACDD) will house the instrument and provide user training for the ITC, while College of Pharmacy and the Office of Research, Innovation and Impact (RII) will support for the service contract. Scheduling of the instrument will be through web-based iLab Organizer, and any conflicts will be resolved through an advisory committee.