Ion Channels as Targets in Drug Discovery: Outlook and Perspectives

Ion channels are ancient proteins, fundamental to basic biology and important targets for disease treatment, in particular, in conditions where imbalance of ionic flux disrupts homeostasis. The remit of the present volume is to present and discuss selected ion channel drugs with potential for clinical translation. Around one-fifth of all drugs act on ion channels, with over 170 available ion channel drugs, 27 of which are listed as WHO Essential Medicines. Such drugs were typically introduced in the “golden age” of modern drug discovery, which covers the latter half of the twentieth century. More recently, however, ion channel drug discovery has somewhat stalled, and it is this issue onto which contributors to this volume seek to shed a potential ray of light. Thus, there are currently over 60 ion channel drugs undergoing clinical trials. Such agents include the small molecules that have dominated ion channel drugs but also newer “biologic” agents, such as peptides and larger antibodies. Alongside this, new technological advances, including in drug engineering strategies, structural biology, and related computational modelling techniques, are now starting to make significant contributions. Moreover, combination of techniques whereby existing drugs are screened against specific phenotypes has utility for all drugs, including those against ion channel diseases with unmet clinical need. Overall, this introductory chapter and the broader volume will discuss and provide evidence that ion channel drug discovery is poised for a renaissance.