title: Ion channels as therapeutic targets: a drug discovery perspective.
abstract: Ion channels are membrane proteins expressed in almost all living cells. The sequencing of the human genome has identified more than 400 putative ion channels, but only a fraction of these have been cloned and functionally tested. The widespread tissue distribution of ion channels, coupled with the plethora of physiological consequences of their opening and closing, makes ion-channel-targeted drug discovery highly compelling. However, despite some important drugs in clinical use today, as a class, ion channels remain underexploited in drug discovery and many existing drugs are poorly selective with significant toxicities or suboptimal efficacy. This Perspective seeks to review the ion channel family, its structural and functional features, and the diseases that are known to be modulated by members of the family. In particular, we will explore the structure and properties of known ligands and consider the future prospects for drug discovery in this challenging but high potential area.
authors.affiliation: Worldwide Medicinal Chemistry, Pfizer Neusentis , The Portway Building, Granta Park, Great Abington, Cambridge, CB21 6GS, UK.
authors.forename: Sharan K
authors.initials: SK
authors.lastname: Bagal
authors.forename: Alan D
authors.initials: AD
authors.lastname: Brown
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cox
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Omoto
authors.forename: Robert M
authors.initials: RM
authors.lastname: Owen
authors.forename: David C
authors.initials: DC
authors.lastname: Pryde
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sidders
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Skerratt
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stevens
authors.forename: R Ian
authors.initials: RI
authors.lastname: Storer
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Swain
mesh_terms: D055808:Drug Discovery; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects*; D008958:Models, Molecular; D010802:Phylogeny
chemical_list: D007473:Ion Channels