WNK Signaling Inhibitors as Potential Antihypertensive Drugs

AlAmri, Mubarak A. and Kadri, Hachemi and Dhiani, Binar Asrining and Mahmood, Shumail and Elzwawi, Abdulrahman and Mehellou, Youcef (2017) WNK Signaling Inhibitors as Potential Antihypertensive Drugs. PEER REVIEW.

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Abstract

Since the discoveryofWNK mutationsthat cause an inherited form of hypertensioninhumans, there has been increasing interest in targeting WNK signaling as anovel strategy for modulating blood pressure. This notion is now supported by numerous mouse modelswith impaired WNK signaling that exhibit reduced blood pressure. Biochemical analyses of the various protein components that make up this signaling pathway have identified anumber of plausible molecular targets that are amenabletotargeting by small molecules. To date, aselection of small-molecule WNKsignaling inhibitors have been identified and have shown promise in suppressing the activity of WNK signaling in cells and in animals. In this Minireview, we briefly discussthe WNK signaling pathway and providean overview of the various druggable targets within this cascade, as well as the different WNK signalinginhibitors discovered to date.

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