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.
Acknowledgements
We gratefully acknowledge Jonathan Sheehan and Jens Meiler (Vanderbilt Center for Structural Biology) for developing the original Kir channel structural model Citation[11] from which was derived.
Financial & competing interests disclosure
The authors are supported by NIH grants 1R21NS5704111 (Jerod S Denton) and 1U54MH084659-01 (Brian A Chauder), an American Heart Association-Southeast Affiliate Beginning Grant-In-Aid (Jerod S Denton), a National Kidney Foundation Postdoctoral Fellowhip grant (Gautam Bhave) and the Vanderbilt Department of Anesthesiology BH Robbins Scholars Program (Daniel Lonergan).The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.