Channelpedia

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


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

Journal, date & volume: Future Med Chem, 2010 May , 2, 757-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20543968

Channelpedia reference in: Kir1.1

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.