Recent advances in combinatorial chemistry together with the development of automated high-throughput screening devices offer enormous opportunity for identification of novel bioactive compounds. Chemical libraries that contain 20,000-100,000 stereochemically diverse compounds are already commercially, and the National Cancer Institute repositories contain vast numbers of cytotoxic compounds that remain uncharacterized. Finally, focused libraries will be generated in a sister core, Core D. A major limitation in the identification of useful compounds is the development of reliable bioassays and the ability to screening these libraries rapidly. Core C will focus on the development of methods for screening, and using these screens to assist COBRE investigators in identifying and characterizing useful compounds. Compounds that inhibit enzymes such as protein kinases, that bind cell receptors, or that inhibit biological processes by binding to previously unidentified molecules, can be identified with the use of high-throughput screens that will be implemented in Core C. Funds provided by the University and the State of Kansas will establish Core C infrastructure. Funds are requested from COBRE for the initial operation of Core C; including support for personnel and consumable supplies. This core will be supervised by experienced senior and junior COBRE program scientists with expertise in the areas of biochemistry, cell biology, molecular biology, and cancer research. The senior investigators will serve to advice and educate junior investigators regarding the utility of this core. The core will be directed by a senior investigator who is active in the development and use of novel bioassays for screening chemical libraries to identify novel anti-mitotic agents and new molecular targets for anti-cancer agents.
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