[DOT 2018] Binding and Functional Analysis -Complementary Approaches in Safety Pharmacology

[DOT 2018] Binding and Functional Analysis -Complementary Approaches in Safety Pharmacology
File Name/Number:
DOT 2018


In vitro pharmacological profiling is an integral part of drug discovery and development, and provides critical information at multiple key decision points in the process. Knowing the in vitro pharmacological safety profile is important for choosing the best potential drug candidate and is a required part of any regulatory filing. In the absence of specific guidelines on safety profile size and content from the regulatory agencies, a group of large pharmaceutical companies published (Bowes et al., 2012) a consensus core of 44 targets that includes G protein-coupled receptors (GPCRs), ion channels, transporters, nuclear hormone receptors, andsome enzymes, all of which showed a clear correlation with observed in vivo toxic effects. There is a consensus that both binding and functional approaches are complementary, and that care needs to be taken to confirm specificity and activity whenusing this type of complementary approach. In accordance with these recommendations, use of both binding and functional assay panels can provide insights into the early identification of off-target interactions that can lead to safety liabilities. In this poster, we compare the results obtained from evaluation of several compounds in binding assays with their profiles in subsequent, analogous functional assays, in order to characterize the correlation between the two assay modalities, using several different target types as exemplars.