Mapping Pathways in Phenotypic Assays Using Chemical Probes
Phenotypic assays using human cell types can help replace animal testing in drug discovery and product development. We can’t trust these assays, however, if we can’t explain why or why not a drug or substance is active. Assay characterization using reference standards can help us do this.
Chemical probes are small molecules designed to interact with specific targets and interfere with their function. These are ideal to use as reference standards, if they are highly selective and specific for their intended targets. The Chemical Probes Portal is helping to ensure that probes are selective and that researchers understand how to use them (e.g. recommended concentrations, applications, etc.).
We have been interested in using chemical probes to standardize how phenotypic assays are characterized. Many researchers are unaware of just how many known pathways and targets are active in their phenotypic assays. They can misinterpret results if their assays are not well characterized.
We have prioritized a set of 17 pathways (and chemical probes) for general purpose characterization of phenotypic assays (see paper here). These include target pathways involved in cell migration, major signaling pathways, autophagy, epigenetic and mitochondrial function and cell metabolism.
These probes were profiled in a panel of human primary cell models (BioMAP® systems available from Eurofins Discovery). To facilitate exploration of these data, see the interactive viz on Tableau Public. Pathways (and corresponding probes) can be selected and data can be sorted to find assays that are most responsive for a given pathway.
