Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.
Future Med Chem. 2012 Apr;4(5):661-79. doi: 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.
离子通道是许多治疗用途药物的靶标，全球离子通道靶向药物的销售额估计约为 120 亿美元。然而，考虑到已经鉴定出编码离子通道亚基的超过 400 个基因，离子通道作为治疗靶点仍然远远没有得到充分利用。这至少部分是由于支持筛选和先导化合物优化的高通量检测技术的局限性所致。最近自动化电生理学的发展是否会纠正这种情况？还有哪些主要的局限性，它们能被克服吗？在本文中，我们回顾了离子通道药物发现的现状，讨论了当前的挑战，并提出了可能有助于未来发现新药的替代方法。
