Shared Resource 10: Medicinal Chemistry (MCSR)

PROJECT SUMMARY – MEDICINAL CHEMISTRY SHARED RESOURCE (MCSR) The MCSR supports scientific endeavors of OSUCCC members to create chemical probes to disrupt molecular pathways implicated in tumor growth, and to work with investigators to identify and create targeted agents against novel therapeutic moieties selected for properties important for preclinical and clinical development. The MCSR was established as a developing shared resource in 2011, and became a full CCSG shared resource in 2015. The MCSR supports investigators conducting preclinical in vitro and in vivo studies by integrating the expertise of multiple disciplines, including medicinal chemistry, process chemistry, computational chemistry, structural biology and molecular pharmacology. Key services are custom synthesis and lead optimization, including structure activity relationship analysis and structure-based optimization. Overall, the MCSR provides a crucial niche service for investigators identifying new therapeutic compounds. The Specific Aims of the MCSR 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 as cancer therapeutics; and 3) as a developing aim, enable screening of small molecules against proteins and whole-cell assays to identify new compounds for further preclinical testing. For this Developing Aim, Dr. Blake Peterson (TT) has been added as co-Director of the MCSR, and the OSUCCC will invest $3M in small molecule screening; these new capabilities will require hiring additional staff and a technical director, purchasing of equipment to conduct screens, and renovation of space. Over the current grant cycle, the MCSR supported 34 investigators (79% OSUCCC members) from all five research programs, including members at Nationwide Children's Hospital, and provided 7,625 hours of service (81.7% to OSUCCC members). The MCSR also contributed to 29 publications (9 > 10 impact factor), 34 users, and 7 NCI grants, including 1 K12, 1 U01, 1 R35, 1 R01, 2 P01s, and 1 P50. Over the next grant cycle, the MCSR will directly support the OSUCCC's strategic priorities for immuno-oncology and translational genomics. It will also support the development of drugs with potential for cancer prevention. The major thrust for the MCSR will be to implement small molecule screening and build the user base to identify novel compounds, and targets by phenotypic screening against cancer pathways, thereby identifying mechanisms of cancer initiation and progression that are central to goals of CB and MCC. The annual budget of the MCSR is $930,296, yet the CCSG request is $80,063. As such, the MCSR seeks only 8.6% budgetary support from CCSG funds.