Therapeutic scope of modulation of non-voltage-gated cation channels.
Although widely regarded as attractive drug targets, less than a tenth of known ion channels are currently commercially exploited as therapeutic targets. Historically, drug discovery efforts on ion channel targets have been encumbered by a lack of molecular and structural information, sub-optimal screening technologies and a paucity of discriminating pharmacological tools. Although challenges remain, recent scientific and technological advances in the area of ion channel research and screening offer the exciting prospect of a new, more-predictive era of ion channel drug discovery. In this article, focusing primarily on non-voltage-gated cation channels, we describe the continuing evolution of approaches to ion channel drug discovery, highlight recent developments in the ion channel field and consider their potential impact on discovering and ascribing function to ion channel targets. We discuss the renaissance of known ion channel targets, such as nicotinic acetylcholine receptors and calcium-activated potassium channels, as well as the emergence of the transient receptor potential (TRP) channels as a gene family of cation channels with broad therapeutic potential.
Li
Su
S
Novartis Institutes for Biomedical Research, Novartis Respiratory Research Centre, Wimblehurst Road, Horsham, West Sussex, UK. su.li@pharma.novartis.com
Gosling
Martin
M
Poll
Chris T
CT
Westwick
John
J
Cox
Brian
B
D000818:Animals; D002412:Cations / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D002412:Cations; D007473:Ion Channels