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Small-molecule modulators of inward rectifier K(+) channels: recent advances and future possibilities

Author:
Bhave, Gautam  Lonergan, Daniel  Chauder, Brian A.  Denton, Jerod S.  


Journal:
FUTURE MEDICINAL CHEMISTRY


Issue Date:
2010


Abstract(summary):

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.


Page:
757---774


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