The process of identifying small molecule hits suitable for subsequent optimization into leads, and eventually candidates is a critical stage of the drug discovery workflow. Historically, the early stages of drug discovery have been based on finding compounds with either the highest activity or the highest affinity against the target of interest, with little consideration for the mechanism of action or the forces driving the binding event. Understanding the kinetics, thermodynamics and how the compound causes its effect in biochemical, biophysical and cellular settings is now viewed as important in identifying the most promising hits that could lead to differentiated lead series. Furthermore, it allows the identification and prioritization of not just a single mechanism, but potentially a range of thoroughly characterized diverse mechanisms, to produce a number of differentiated options to ultimately achieve the desired biological effect in vivo. This poster will describe how the assay development and screening group at Concept Life Sciences sets up screening cascades to obtain as much information as possible on compound-target interactions in order to drive better SAR decisions in early drug discovery programs.