Fluorescence‐Based HTS Assays for Ion Channel Modulation in Drug Discovery Pipelines

Abstract

Ion channels represent a druggable family of transmembrane pore‐forming proteins with important (patho)physiological functions. While electrophysiological measurement (manual patch clamp) remains the only direct method for detection of ion currents, it is a labor‐intensive technique. Although automated patch clamp instruments have become available to date, their high costs limit their use to large pharma companies or commercial screening facilities. Therefore, fluorescence‐based assays are particularly important for initial screening of compound libraries. Despite their numerous disadvantages, they are highly amenable to high‐throughput screening and in many cases, no sophisticated instrumentation or materials are required. These features predispose them for implementation in early phases of drug discovery pipelines (hit identification), even in an academic environment. This review summarizes the advantages and pitfalls of individual methodological approaches for identification of ion channel modulators employing fluorescent probes (i. e., membrane potential and ion flux assays) with emphasis on practical aspects of their adaptation to high‐throughput format.