Lead optimization is a complex, non-linear process. During this stage of drug discovery, the chemical structure of a confirmed hit is refined to improve its drug characteristics with the goal of producing a preclinical drug candidate.
Typically, confirmed hits are evaluated in secondary assays, and a set of related compounds, called analogs, are synthesized and screened. The testing of analog series results in quantitative information that correlates changes in chemical structure to biological and pharmacological data to establish structure-activity relationships (SARs).
Other secondary screens are used to test a range of compound concentrations to assess the dose dependence of the assay's readout. Typically, this dose-response is expressed as an IC50 in enzyme-, protein-, antibody-, or cell-based assays or as an EC50 in in vivo experiments. The shape of a dose-response curve often provides information about the mechanism of action.
Today, secondary screens are often focused on early safety assessment and involve a series of standard assays that evaluate toxicity.
Molecular Devices offers a range of products that are particularly well suited for secondary screening assays, including technologies for cell-based assay readouts, high content analysis, automated patch clamp, and label-free analysis. Please select among the links below to learn more.