title: Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities.
abstract: Inward rectifier potassium (Kir) channels have been postulated as therapeutic targets for several common disorders including hypertension, cardiac arrhythmias and pain. With few exceptions, however, the small-molecule pharmacology of this family is limited to nonselective cardiovascular and neurologic drugs with off-target activity toward inward rectifiers. Consequently, the actual therapeutic potential and 'drugability' of most Kir channels has not yet been determined experimentally. The purpose of this review is to provide a comprehensive summary of publicly disclosed Kir channel small-molecule modulators and highlight recent targeted drug-discovery efforts toward Kir1.1 and Kir2.1. The review concludes with a brief speculation on how the field of Kir channel pharmacology will develop over the coming years and a discussion of the increasingly important role academic laboratories will play in this progress.
authors.affiliation: Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Bhave
authors.forename: Daniel
authors.initials: D
authors.lastname: Lonergan
authors.forename: Brian A
authors.initials: BA
authors.lastname: Chauder
authors.forename: Jerod S
authors.initials: JS
authors.lastname: Denton
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D006801:Humans; D008958:Models, Molecular; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D054852:Small Molecule Libraries