Chapter 1:HTS Methods: Assay Design and Optimisation

High throughput screening (HTS) remains the key methodology for finding hit and lead compounds within the pharmaceutical industry and also, recently, in the academic drug discovery community. HTS has changed significantly in AstraZeneca over the last 15–20 years with a massive expansion of the number of compounds available to screen, increasing industrialisation and automation of the process in order to cope with larger numbers of compounds, and more recently, the running of screens from external collaborators via open innovation initiatives. In this chapter we will discuss how this approach to HTS has been developed within AstraZeneca and pay particular attention to how the optimisation and validation of the wide spectrum of assays that we have to deal with in our group is done. We will discuss how we accept assays into HTS from our assay development groups and describe how these assays are validated and optimised for use as an HTS screen.