Assay Validation Using Chemical Probes

Exploring Target Function Using Chemical Probes in Phenotypic Assays

Chemical probes are small molecules that interact with specific targets. Characterizing phenotypic assays with chemical probes can:

(1) Identify which targets (and pathways) are active in a given assay

(2) Facilitate mechanism of action studies

(3) Build our knowledge of human disease biology

(4) Increase our confidence in the specificity of the chemical probes themselves

Phenotypic assays by nature detect the activities of multiple targets and pathways.  This makes them useful for novel drug discovery. However, if we need to know the mechanism of action of an active test agent, this can be a challenge. Characterization of assays using chemical probes helps suggest potential mechanisms and guide the process of mechanism deconvolution.

Comparing the activities of chemical probes to each other across phenotypic assays can build our knowledge of human biology.  Such studies can reveal how target biology differs depending on cellular and tissue context (e.g. cell types and activation settings).  This information is key to understanding efficacy and safety mechanisms.  These results also help us map phenotypic assays to clinical indications of interest.

Comparative studies of chemical probes tested across standardized assays can also help advance the development of chemical probes.  Patterns of probe activities can help confirm the selectivity and specificity of new probes.

All of these benefits of using chemical probes in phenotypic assays are enhanced if results are accessible and understandable to diverse stakeholders.  We are working on interactive visualizations of published reference data on chemical probes tested in phenotypic assays.

See our case study showcasing an interactive visualization of a published data set using a set of chemical probes selected as general reference standards for key target pathways: Mapping Pathways in Phenotypic Assays Using Chemical Probes