Ion Channels as Therapeutic Drug Targets

Abstract

Ion channels comprise a large and diverse family of proteins that control many physiological functions. For this reason, a number of inherited diseases result from mutations in specific genes that alter the functions of given ion channels. Drugs used to treat a variety of pathophysiological conditions derive their benefits from interacting with specific ion channel(s), and efforts to develop novel ion channel drugs that would address unmet clinical needs are ongoing in pharmaceutical, biotech, and academic institutions. During the past period of time, major developments in functional screening technologies have afforded the study of these proteins in high‐density formats. In addition, a large body of information concerning the structure of different ion channels has become available. In some cases, intimate details of the interactions between drugs and ion channels have been obtained, which may help with designing more potent and selective ion channel modulators. Although a number of ion channel modulators have entered clinical development, lack of therapeutic efficacy or toxicity issues have caused termination of the development of many of these agents. Nonetheless, with all accumulated experience and new technological advancements, expectations are high for the successful development of novel ion channel modulators in the future.

Structural modeling of peptide toxin–ion channel interactions using RosettaDock

“…Due to their physiological relevance, VGICs are important molecular targets for treating a large diversity of diseases 7,8 . Achieving high subtype selectivity for molecules targeting specific VGICs is of primary importance to not impair crucial physiological functions mediated by off‐target channels.…”

Structural Modeling of Peptide Toxin - Ion Channel Interactions using RosettaDock

“…Due to their physiological relevance, VGICs are important molecular targets for treating a large diversity of diseases (Garcia and Kaczorowski, 2021; Wulff et al, 2019). Achieving high subtype selectivity for molecules targeting specific VGICs is of primary importance to not impair crucial physiological functions mediated by off-target channels.…”