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Updated: Feb 20, 2026

High-throughput Screening for Small-molecule Modulators of Inward Rectifier Potassium Channels
Published on: January 27, 2013
The therapeutic potential of targeting the Kir1.1 (renal outer medullary K+) channel
Birgit T Priest1, Alexander Pasternak2
1Department of Quantitativce Biology, Eli Lilly & Co, Indianapolis, IN, USA.
Abstract:
Kir1.1 (renal outer medullary K+) channels are potassium channels expressed almost exclusively in the kidney and play a role in the body's electrolyte and water balance. Potassium efflux through Kir1.1 compliments the role of transporters and sodium channels that are the targets of known diuretics. Consequently, loss-of-function mutations in men and rodents are associated with salt wasting and low blood pressure. On this basis, Kir1.1 inhibitors may have value in the treatment of hypertension and heart failure. Efforts to develop small molecule Kir1.1 inhibitors produced MK-7145, which entered into clinical trials. The present manuscript describes the structure-activity relationships associated with this scaffold alongside other preclinical Kir1.1 blockers.
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