Combining Optical Approaches with Human Inducible Pluripotent Stem Cells in G Protein-Coupled Receptor Drug Screening and Development

Abstract

Drug discovery for G protein-coupled receptors (GPCRs) stands at an interesting juncture. Screening programs are slowly moving away from model heterologous cell systems such as human embryonic kidney (HEK) 293 cells to more relevant cellular, tissue and whole animal platforms. Investigators are now developing analytical approaches as means to undertake different aspects of drug discovery by scaling into increasingly more relevant models all the way down to the single cell level. Such approaches include cellular, tissue slice and whole animal models where biosensors that track signaling events and receptor conformational profiles can be used. Here, we review aspects of biosensor-based imaging approaches that might be used in inducible pluripotent stem cell (iPSC) and organoid models, and focus on how such models must be characterized in order to apply them in drug screening.

Drug Screening with Genetically Encoded Fluorescent Sensors: Today and Tomorrow

“…Commonly used cell cultures, like HEK 293 cells, are often physiologically irrelevant. Given these considerations, the use of primary cultures or IPCs-derived cultures might decrease the attrition rate of drug screening assays [ 63 ].…”

Conserved Expression of Nav1.7 and Nav1.8 Contribute to the Spontaneous and Thermally Evoked Excitability in IL-6 and NGF-Sensitized Adult Dorsal Root Ganglion Neurons In Vitro

“…Substrate integrated microelectrode arrays (MEAs), alternatively, provide non-invasive and long-term measurements recorded simultaneously from a large population of cells. The use of an MEA platform may allow the development of in vitro phenotypic screening assays that utilize cellular excitability for screening potent small molecule inhibitors against “pain” channels and support efforts in identifying analgesic compounds [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ]…”