The major goals of the Bioinformation and Cell-based Assay Core are to provide computational resources to aid in the design, analysis, and therapeutic optimization of dual specificity phosphatase inhibitors and antimitotic agents and to perform cell-based, high-information content analyses on prioritized compounds from other subprojects to aid in the selection of candidates for preclinical evaluation by Core C. The Core thus assumes a central location between the chemistry, biology, and preclinical assay groups. To achieve these goals, the Core will perform four main functions: 1) data warehousing; 2) data mining and molecular modeling 3) high-information content, cell-based analyses and; 4) in vitro analysis of microtubule perturbing agents. Data mining will be accomplished through a series of hierarchical SAR and QSAR techniques to analyze the large and diverse learning sets of information associated with the two targeted biological activities from other subprojects. Cell-based analyses will make extensive use of the Core's existing high-throughput, cell-based assay and analysis capabilities including automated liquid handling, fluorescence-based multiparametric assays, and automated image acquisition and batch image processing. The Specific Tasks of this Core are 1) To provide informatics for the Program Project by maintaining a central, electronic, program-accessible repository of chemical and biological data; 2) To facilitate the identification of new lead structures by creating models of molecular requirements for prioritized compounds through in silico screening of in-house combinatorial libraries or outside compound databases. 3) To perform multiparametric analyses, including gowth inhibition studies, of prioritized compounds in intact cells, either alone or in combination with existing chemotherapeutic agents. 4) To evaluate the in vitro tubulin/microtubule perturbing activities of library components.
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