Chapter 27 The Application of Transcriptional Profiling in Model Connectivity and Lead Assessment in Drug Discovery

Publisher Summary Transcriptional profiling, also known as transcriptomics or mRNA expression profiling, has several useful applications in the field of drug discovery. Most recently, there is recognition of its utility for making the connection between compounds that have been optimized through in vitro assays and their activity on the in vivo biology of the disease process. After outlining the state of the art in obtaining and interpreting transcriptional profiling data, two additional aspects of this tool are reviewed. This chapter discusses transcriptional responses in disease models as biomarkers, and their connection to potential pharmacological treatments for disease. It also discusses the characterization of transcriptional selectivity profiles for potential drugs by comparison of their transcriptional changes. This chapter illustrates with literature examples how transcriptional profiling of pharmacological response can be used to address important issues in drug discovery. Recent reviews have explored the use of transcriptional profiling in mechanism of action studies on mammalian models, yeast and in antibiotics discovery and development. The application of transcriptional profiling as a measure of response to toxicants in model systems, and the use of these responses to classify and predict toxicity in new drug candidates, is termed “toxicogenomics,” which is also reviewd in the chapter. .