Abstract
This chapter first explores what types of drug targets, treatment options, and screening strategies are the most successful to discover new small molecule drugs. Although target-based screening has certainly led to many successes, it failed more than expected, and there is now a renewed interest in phenotypic screening. Together with new capabilities to handle thousands of animals like zebrafish in an automated way, this results in an increased demand for target deconvolution. In this chapter the current most frequent methods for target identification, deconvolution, and validation are summarized in a very systematic way for a primarily nonspecialist audience. Methods described are affinity chromatography, haploinsufficiency profiling in yeast, analysis of resistant mutations, siRNA, yeast three-hybrid systems, DNA microarrays, comparative profiling, systems biology, analysis of the pathophysiology, and the study of existing drugs. A comparative overview table is provided.
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