Ultra-HTP Multiplex Approach to Small Molecule Screens

描述（由申请人提供）：本提案的更大目标是将小分子筛选技术商业化，该技术可以大大提高新的先导候选药物上市的速度。在这里，我们建议完善一种技术，允许大规模并行多重（MPM）屏幕的小分子，同时解决多个目标，一个商业化的筛选格式。该方法有能力从一个单一的筛选操作的数量级增加输出。它的额外好处是不仅定义命中，而且同时定义命中对一组生物途径的特异性。该项目的第一阶段将对该技术进行三项明确的改进（目标1），并使用临床相关的化疗药物和人类神经胶质瘤细胞验证该技术（目标2）。探针或先导化合物，用于药物开发，跨越细胞中广泛的分子靶点。在该阶段的工作中，已知参与介导临床观察到的对化疗剂的生物反应的基因的鉴定将证明将该方法应用于高通量形式可能产生疾病相关试剂。

DESCRIPTION (provided by applicant): The larger objective of the present proposal is to commercialize a small molecule screening technology that can vastly improve the rate at which new lead candidates are brought to market. Here we propose to refine a technology allowing massively parallel multiplex (MPM) screens for small molecules that address multiple targets simultaneously, to a commercializable screening format. The approach has the power to increase the output from a single screening operation by orders of magnitude. It has the additional benefit of defining not only hits but, simultaneously, the specificity of the hits to a set of biological pathways. Phase I of this project will implement three defined improvements to the technology (Goal 1) and validate the technology using a clinically relevant chemotherapeutic and human glioma cells (Goal 2).Narrative The technology to be exploited here seeks to tap the commercial potential of an extremely broad based biological screen that will identify chemical compounds that act as bio-probes or lead compounds for drug development across a broad range of molecular targets in the cell. In this phase of the work, identification of genes known to be involved in mediating the clinically observed biological responses to a chemotherapeutic agent will demonstrate that the application of this approach to a high throughput format is likely to yield disease relevant reagents.