Enzyme-Based Screens in HTS

High throughput screening and the subsequent hit evaluation phase are critical components of target based drug discovery. Identification of suitable lead material remains a key milestone in any antibacterial strategy, and while target-based drug discovery has proven effective for a number of disease areas, the success rate of this approach has been challenged for antibacterial targets [23]. While there is always a component of luck in matching the right compound file with the chosen target, it is clear that careful and thoughtful assay design, execution, and hit evaluation can tilt the odds in favor of finding quality inhibitors that enable late stage drug discovery. In contrast, poorly designed assays and inadequate hit evaluation processes invariably result in the identification of questionable leads that require extensive resources and time to evaluate and usually have low probabilities for success. This chapter outlines the generic process from building a suitable assay for high throughput screening to the critical factors in selection of lead material for focused drug discovery prosecution.