This Core is focussed on the discovery of new anticancer agents; as opposed to Project 2 which evaluates the nature and the worth of the discovery, and develops it further. This Core is directed towards the discovery of new anticancer agents against Colon, Lung, and an MDR-Mammary Adenocarcinoma. The central element of his project is an in vitro assay which defines the specificity of test compounds in terms of their cytotoxic activity in vitro against a leukemia, murine and human solid tumors (colon, lung, MDR-breast), and normal cells. Agents with preferential cellular selectivity for the solid tumors will be evaluated against these same tumors in vivo (in SCID mice for human tumor assessment of therapeutic efficacy). The test agents will be synthetic organic compounds provided by Eli Lilly Corp. (5,000/year) and Sanofi Winthrop Pharmaceutical Corp. (1,500/year). Depending upon the activities seen in the first evaluation in tumor-bearing mice (this Core), analogs of the discoveries are acquired and progress through the discovery assays in an attempt to select improved agents, the pharmacophoric pattern, and the active core-molecule (termed the """"""""minimum active structure""""""""). The structure-activity relationship (QSAR) studies in Project 3 will help guide the analog selection process.
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