EFFICIENT CHARACTERIZATION OF KINASE INHIBITORS USING LeadCode TECHNOLOGY

The identification of protein targets for organic small molecules, and characterization of these chemical compounds, is of fundamental importance for drug discovery research. Here we describe the application of LeadCode TM technology, developed by GPC Biotech for the proteome-wide identification of protein targets and array-based profiling of kinase inhibitors. LeadCode TM utilizes yeast-three-hybrid technology, an established system for studying protein-small molecule interactions with an optimised methotrexate-based chemical dimerizer. This technology has been developed as a tool for screening human cDNA libraries to identify targets of kinase inhibitors, and to diminish the risk of failure of drug candidates in clinical trails due to possible side effects. For target validation and rapid comparative profiling of kinase inhibitors we set up an array-based screening system. Protein kinases play a crucial role in many disease areas and kinase inhibition has become a major medical research area. Many pharmaceutical companies have potential drug candidates in their pipeline, but there is limited knowledge on the selectivity and specificity of those compounds which is very important for a fast and streamlined development of new potent and safe drugs. This screening-technology is a powerful tool for discovery of novel interactors and lead optimisation by generating compound-specific " target fingerprints ". Here we present the application of LeadCode TM technology for identification of kinase inhibitor targets and subsequent profiling of this small molecule. Hence a subset of human kinases has been screened with several novel and well known kinase inhibitors. With this semi-automated technology, a fast profiling of kinase inhibitors is possible, profiting from the selectivity and high sensitivity of this system. LeadCode TM represents a convenient method for the evaluation, optimisation and development of new drug leads.