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Small-molecule modulators of inward rectifier K+ channels: recent advances and future possibilities Bhave G; Lonergan D; Chauder BA; Denton JSFuture Med Chem 2010[May]; 2 (5): 757-74Inward 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.|Animals[MESH]|Drug Discovery/*methods/trends[MESH]|Humans[MESH]|Models, Molecular[MESH]|Potassium Channels, Inwardly Rectifying/*agonists/*antagonists & inhibitors/chemistry/metabolism[MESH]|Small Molecule Libraries/*chemistry/*pharmacology[MESH] |
