Nuclear receptors act as ligand-activated transcription factors translating ligand signals into changes in gene expression. The 48 members of the superfamily of nuclear receptors identified so far are involved amongst others in maintenance of metabolic balance, inflammation, and cancer. Thus, they hold enormous potential for drug discovery and some nuclear receptors are experiencing considerable academic and industrial interest. Nuclear receptor modulator discovery requires reliable, robust, and economic test systems that allow for high throughput. In this chapter, we discuss the principle, strengths, and advantages of hybrid reporter gene assays for nuclear receptor focused drug discovery and describe how they can be developed, established, and validated.
Keywords: Drug discovery; Gal4; Nuclear receptor modulators; Screening techniques; Transactivation assay.