SPECIAL TOPICS IN DRUG DISCOVERY

Abstract

Autobioluminescent cellular models are emerging tools for drug discovery that rely on the expression of a synthetic, eukaryotic‐optimized luciferase that does not require an exogenous chemical substrate to produce its resultant output signal. These models can therefore self‐modulate their output signals in response to metabolic activity dynamics and avoid the sample destruction and intermittent data acquisition limitations of traditional fluorescent or chemically stimulated bioluminescent approaches. While promising for reducing drug discovery costs and increasing data acquisition relative to alternative approaches, these models have remained relatively untested for drug discovery applications due to their recent emergence within the field. This chapter presents a history and background of these autobioluminescent cellular models to offer investigators a generalized point of reference for understanding their capabilities and limitations and provides side‐by‐side comparisons between autobioluminescent and traditional, substrate‐requiring toxicology screening platforms for pharmaceutically relevant three‐dimensional and high‐throughput screening applications to introduce investigators to autobioluminescence as a potential new drug discovery toolset.