Generic Fluorescent HTS Assay for Protein Kinases

DESCRIPTION (provided by applicant): There are more than 400 distinct protein kinases encoded in the human genome; elucidating their role in disease and identifying selective inhibitors is a major pharma initiative. Kinase malfunction has been linked to all of the most important therapeutic areas, including cancer, cardiovascular diseases, inflammation, neurodegenerative diseases, and metabolic disorders. Moreover, clinical validation of kinases as drug targets has recently been shown in the cases of Herceptin and Gleevec, which inhibit aberrant tyrosine kinases that contribute to breast cancer and leukemia, respectively. High throughput screening (HTS) - the parallel testing of many thousands of compounds for interaction with a drug target - has become the dominant mode of drug discovery. The total market for HTS assay reagents in 2003 was over $500M, and approximately 20% of screening was done on protein kinases. Despite the high level of interest, shortcomings with the current assay methods are hampering efforts to incorporate new kinases into HTS programs and to compare inhibitor profiles for different kinases. To overcome these technical hurdles we propose to develop a universal kinase assay method based on BellBrook Labs' proprietary Transcreener(tm) platform. The assay relies on a competitive fluorescence polarization-based immunoassay for detection of adenosine diphosphate (ADP), a product of all kinase reactions. The Transcreener(tm) kinase assay will accelerate efforts to define kinase substrate specificity and to identify novel inhibitors by providing a universal catalytic assay that can be used with any kinase and any acceptor substrate.