Ultra-HTP Multiplex Approach to Small Molecule Screens

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 te chnology 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 or ders 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 va lidate 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 response s to a chemotherapeutic agent will demonstrate that the application of this approach to a high throughput format is likely to yield disease relevant reagents.