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Ion channel drug discovery: challenges and future directions

    A Wickenden

    Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA

    ,
    B Priest

    Eli Lilly & Co, 355 East Merrill, Indianapolis, IN 46225, USA

    &
    G Erdemli

    * Author for correspondence

    Center for Proteomic Chemistry, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, USA.

    Published Online:https://doi.org/10.4155/fmc.12.4

    Ion channels are targets of many therapeutically useful agents, and worldwide sales of ion channel-targeted drugs are estimated to be approximately US$12 billion. Nevertheless, considering that over 400 genes encoding ion channel subunits have been identified, ion channels remain significantly under-exploited as therapeutic targets. This is at least partly due to limitations in high-throughput assay technologies that support screening and lead optimization. Will the recent developments in automated electrophysiology rectify this situation? What are the other major limitations and can they be overcome? In this article, we review the status of ion channel drug discovery, discuss current challenges and propose alternative approaches that may facilitate the discovery of new drugs in the future.

    Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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