Enhanced Drug Discovery: Utilizing a 3D Spheroid Model and Live-Cell Analysis for Compound Profiling

Assessing the activity profile of a compound is crucial in any drug discovery strategy, especially when profiling large numbers of compounds (ranging from 100 to 100,000) in early-stage programs. Compound screening evaluates various parameters, including changes in cellular morphology and biochemical characteristics after treatment, as well as the effects of drugs in reversing these changes.¹ Phenotypic screening is commonly used for this profiling, allowing the quantification of cell function as an alternative to traditional target-based screening.² Traditional methods often focus on assessing direct target interactions through binding affinity, usually lacking functional potency measurements.

In this application note, we describe the use of live-cell analysis for kinetic, brightfield and fluorescent measurements of spheroid growth and viability in response to a library of 880 FDA-approved drugs. The data showcases the initial single concentration screening phase, assessing the quantification of these two parameters and how they provide information on compound activity. Identified compounds of interest are then further investigated for full responses and compared to data from a monoculture 2D assay.