Phenotypic chemical biology for predicting safety and efficacy

- Improved clinical relevance of screening assays increases the quality of new drugs.
- Modern drug discovery combines phenotypic and target-based screening approaches.
- Chemical biology applied to phenotypic assays can establish clinical relevance.
- Drug mechanisms can be identified by analysis of large chemical biology data sets.
- Phenotypic chemical biology advances our understanding of disease biology.
- Understanding disease biology is critical for improving pharmaceutical productivity.

Phenotypic assays using in vitro cell cultures to forecast compound effects in people are transforming pharmaceutical research and contribute to alternative methods for chemical safety testing. How these assays are validated for human disease relevance is a critical factor for developing more predictive assays. Chemical biology, using drugs as well as target-selective chemical probes, is a direct and efficient approach for establishing disease relevance. Chemical probes can connect information across assays and associate targets to clinical effects. When applied at scale, phenotypic chemical biology advances our understanding of drug and toxicity mechanisms enabling construction of disease outcome pathways. To improve the physiological relevance of phenotypic assays, standardized testing of a curated set of phenotypic pathway probes can provide a higher level of validation for phenotypic assay best practices.

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