molecules of the month

The Merck ROMK potassium channel blocker, MK-8153, is a backup development candidate to MK-7145, whose development as a diuretic was terminated after a Ph. Ib study due to lack of efficacy. Traditional loop diuretic drugs such as furosemide inhibit the Na-K-Cl co-transporter, but carry the risk of life-threatening urinary potassium loss. ROMK is a K channel that feeds K ions to NKCC, facilitating Na absorption, and ROMK inhibitors act as diuretics in animal models without the same levels of potassium loss. Objectives for the backup molecule included a longer half-life and better permeability to enable an extended release formulation. A lower peak-to-trough ratio was thought to be desirable since high peak-to-trough ratios lead to rebound sodium retention and reduced PD over…