Challenge of Traditional Assays
An understanding of the diverse binding modes of kinase inhibitors and their effects on biological systems can provide researchers with important clues regarding the effective design of new drugs.
At this time, however, efficient, broadly applicable high-throughput screening (HTS) analysis of kinase inhibitors is primarily achieved through kinase activity assays. Activity assays, by their very nature, are only useful for measuring inhibition of active kinase preparations, which means that analysis is limited to active targets for which suitable in vitro substrates have been identified.
An alternative to the activity assay involves directly measuring the binding of small molecules to the kinase under investigation. Such binding assays can be used to study kinases prepared both in active and nonactive states. This allows the researcher the freedom to choose the specific kinase state to be targeted in HTS campaigns. Moreover, the mechanisms of newly identified inhibitors can be evaluated by measuring binding characteristics to multiple states of the kinase target.