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Small Molecules Targeting Kidney ClC-K Chloride Channels: Applications in Rare Tubulopathies and Common Cardiovascular Diseases

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Given the key role played by ClC-K chloride channels in kidney and inner ear physiology and pathology, they can be considered important targets for drug discovery. Indeed, ClC-Ka and ClC-Kb… Click to show full abstract

Given the key role played by ClC-K chloride channels in kidney and inner ear physiology and pathology, they can be considered important targets for drug discovery. Indeed, ClC-Ka and ClC-Kb inhibition would interfere with the urine countercurrent concentration mechanism in Henleā€™s loop, which is responsible for the reabsorption of water and electrolytes from the collecting duct, producing a diuretic and antihypertensive effect. On the other hand, ClC-K/barttin channel dysfunctions in Bartter Syndrome with or without deafness will require the pharmacological recovery of channel expression and/or activity. In these cases, a channel activator or chaperone would be appealing. Starting from a brief description of the physio-pathological role of ClC-K channels in renal function, this review aims to provide an overview of the recent progress in the discovery of ClC-K channel modulators.

Keywords: clc chloride; chloride channels; clc; molecules targeting; small molecules

Journal Title: Biomolecules
Year Published: 2023

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