Drug discovery based on target molecules may represent the primary focus of the pharmaceutical industry. The existence of compensation mechanisms and feedback pathways in the complex cellular environment usually leads to a significant reduction in the targeting and therapeutic efficacy of the drugs, even though the drug has been previously demonstrated to be effective at the molecular level in vitro. The discovery of phenotypic drugs initially requires the identification of disease-specific features. Cell phenotypic screening has regained momentum and is receiving widespread attention.
Due to advances in both high-throughput phenotypic assay techniques and target identification methodologies, cell phenotype has been emerging as an attractive approach for screening and profiling drugs in native cells. They could provide rich information, real-time kinetics, flexible assays and high throughput in screening that are common to all phenotypic assays. Single-cell measures have been used to phenotype individual cells within tissues in each experiment. However, the field is moving toward multimodal measurements from the same cell to enhance feature quantifications and give a richer picture of a cell's phenotype at any given moment.
Cell phenotype analysis plays a major role in promoting drug discovery and development. As a screening method to assess the biological activity of compounds based on cell or organism level, phenotypic screening could shorten the period of drug discovery of disease. Phenotype-based drug screening programs involve endpoints of using simple cytotoxicity-based screens, coculture and organoids to animal model, making it a very flexible and robust setup. Advances in imaging, analysis software and target techniques offer a strong reason for selecting this approach in drug discovery programs.