Chapter 5: Complex Primary Human Cell Systems for Drug Discovery Check Access

Phenotypic or biofunctional assays play an important role in drug discovery by helping to bridge the gap between high-throughput, target-based screening assays used for compound identification and more physiologically relevant in vivo disease models used for preclinical development. We have developed a standardised panel of phenotypic assays using primary human cells and co-cultures that model tissue and disease biology for characterization of drug leads. Here we show application of these assays for characterisation of clinical stage kinase inhibitors for rheumatoid arthritis, the recently approved JAK kinase inhibitor, tofacitinib, and the SYK kinase inhibitor, fostamatinib. We demonstrate how profiling in this assay panel can relate to clinical effects, both efficacy and safety related.