CHAPTER 2: High-Throughput Screening

Ion channels are a class of proteins that are attractive human, animal, and crop health targets. Ion channels can be considered high-gain (physiologically speaking), high-reward (therapeutic benefit) and high technology (difficult assay development) drug targets. Ion channels are attractive therapeutic targets because they often have high control gain in physiological systems; opening or blocking many of the ion channels studied to date has a large effect on the function of the muscle, nerve, or cell containing the channels. The major issue confronting ion channel drug development teams is safety as the same or closely-related ion channels are often widely distributed in the heart and CNS, and activity at these channels needs to be minimal. This chapter reviews the history of ion channel HTS techniques, using examples from the authors’ work to illustrate how the necessary approaches yield good results, and describing in numerical detail their approach to assay development and full library HTS for selected examples in as much detail as possible.