COMPLEMENTATION ASSAY TO SCREEN FOR KINASE INHIBITORS

DESCRIPTION (provided by applicant): Protein kinases are a family of enzymes that play a pivotal role in signal transduction and have become an important molecular target for drug development. In our phase I SBIR grant, we developed a universal protein kinase assay which employs our proprietary CEDIA(r) technology and consists of measuring the competitive binding of staurosporine, a universal protein kinase ligand, to individual recombinant protein kinases. The non-radioactive assay was able to identify inhibitors of protein kinase C, and was adapted to screen small molecule libraries against a proprietary orphan serine/threonine protein kinase in collaborative studies with Chiron. To demonstrate the full utility of this assay, in this phase II SBIR grant, we propose to employ our assay to screen a small molecule library for inhibitors of two therapeutically important serine/threonine protein kinases, IkB kinase and beta-adrenergic receptor kinase which are targets for the development of drugs to treat cancer, inflammatory disorders and tolerance development and for which no drug screening assays are currently available. We propose to develop a novel assay to "measure the compartmental translocation of protein kinases to identify drugs that could impede selective functions of individual protein kinases without inhibiting their active site. Accomplishing these goals will allow us to provide a portfolio of assays for protein kinase drug discovery that we will commercialize to pharmaceutical, biotechnology and functional genomics companies. We have already initiated collaborations with Chiron and a major pharmaceutical company to employ our technology for their protein kinase drug discovery efforts and expect that further validation of the technology by accomplishing the goals of this grant application will increase the scope of biopharmaceutical and genomic-based companies that we can commercialize the technology.