SUMMARY The development of useful chemical probes generally requires careful optimization of initially discovered agent, whether they arise by modifying an existing agent, from high throughput screening or fragment-based methods, or through a computational study. The purpose of Core D is to provide synthetic chemistry support, including the validation of hit compounds obtained through high-throughput screening, quality control and analysis of compounds, synthesis of compounds unavailable commercially but needed by researchers, structure-activity relationship studies based on HTS campaigns, and optimization of fragment binders. Although most libraries used for screening and fragment efforts will continue to be commercially procured, the MC Core will continue ongoing efforts to create novel libraries for screening and fragment work. The work of the MC Core will be integrated into the suite of core lab activities. For example, hit selection and clustering will be done in conjunction with Cores B and C, compound management and storage in close cooperation with the HTS component of Core C, and analog design in collaboration with Core C.