CORE--BIOINFORMATION AND CELL-BASED ASSAY

生物信息和基于细胞的检测核心的主要目标是提供计算资源，以帮助设计、分析和优化双特异性磷酸酶抑制剂和抗有丝分裂剂的治疗，并对其他子项目的优先化合物进行基于细胞的高信息含量分析，以帮助核心C选择临床前评价的候选药物。因此，核心假设化学、生物学和临床前检测组之间的中心位置。为了实现这些目标，核心将执行四个主要功能：1）数据仓库; 2）数据挖掘和分子建模3） 高信息含量、基于细胞的分析; 4）微管干扰剂的体外分析。数据挖掘将通过一系列的分层SAR和QSAR技术来完成，以分析与其他子项目的两个目标生物活动相关的大量和不同的学习信息集。基于细胞的分析将广泛利用Core现有的高通量、基于细胞的测定和分析能力，包括自动化液体处理、基于荧光的多参数测定以及自动化图像采集和批量图像处理。本核心的具体任务是：1）通过维护一个中央的、电子的、可供程序访问的 化学和生物学数据库; 2）通过对内部组合库或外部化合物数据库进行计算机筛选，为优先化合物创建分子需求模型，从而促进新先导结构的鉴定。 3)进行多参数分析，包括生长抑制研究，在完整细胞中的优先化合物，单独或与现有的化疗药物组合。 4)评价文库组分的体外微管蛋白/微管干扰活性。

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.