Many kinases, such as protein kinase C (PKC), the cyclin-dependent kinase family, and protein tyrosine kinases (PTKs), play a significant role in the generation and development of tumors. Specific small molecule inhibitors of these kinases are of great value as potential therapeutic drugs, and as research tools to investigate carcinogenesis. The aim of this proposal is to develop assays for inhibitors of these kinases to be used in an ultra-high throughput chip-based microfluidic screening system. Many large combinatorial libraries are now commercially available for screening. However, with conventional methods the reagent consumption to carry out large numbers of assays is prohibitively expensive. We have developed a novel microfluidic technology that enables high-throughput screening with very high speed and very low reagent consumption (nL per test). It combines micromachined fluidic networks and active electrokinetically-driven control over material movement within these networks. The first assay we intend to develop is for PKC inhibitors.Proposed Commercial Application:There is great value in any tool that improves or accelerates the process of drug discovery and characterization. Caliper's rapid assays with extremely low reagent consumption, together with the availability of combinatorial libraries of small molecules, have commercial significance in the drug discovery process.
Thesaurus Terms:drug screening /evaluation, enzyme inhibitor, method development, protein kinase C chemical registry /resource, fluid flowNATIONAL CANCER INSTITUTE
