Sequence-based protein kinase inhibition: applications for drug development.

Nearly a century ago, Paul Ehrlich proposed his lock and key theory that has remained one of the cornerstones of rational drug development. Disrupting or enhancing the interaction between a ligand and its substrate is the basis for numerous drugs targeting signal transduction processes. Much of drug discovery is based on finding molecular mimics that resemble either the lock or key of a given ligand-substrate pair. The challenge of drug development is the rapid and efficient identification of mimics that are highly selective and specific for the targeted interaction. Scientists associated with Keryx Biopharmaceuticals (New York, NY, USA) have developed two drug discovery technologies, based on molecular mimicry, that combines rapid development of drug candidates and identification of potential biomarker targets for selected indications. KinAceTM is a platform technology for the protein-sequence-based development of small peptide-derived kinase inhibitors developed by Shmuel A. Ben-Sasson at the Hebrew University in Jerusalem and Keryx Biopharmaceuticals (1,2). KinScreenTM is a method for identifying novel target kinases utilizing peptides developed via the KinAce technology. Peptides directed against specific kinases are tested in a series of biomarker assays that serve as in vitro models for a variety of diseases or pathologic processes including cancer, diabetes, angiogenesis, and immune disorders. The advantage of this technique is that it identifies both kinase biomarker targets with potential therapeutic applications and drug candidates suitable for further development (1).