Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition

Jinwei Zhang, Xianming Deng, Kristopher T. Kahle (Lead / Corresponding author)

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)
197 Downloads (Pure)

Abstract

The with-no-lysine (K) WNK kinases are master regulators of the Na+-(K+)-Cl- cotransporters, including the renalspecific NCC and NKCC2 cotransporters. The discovery of WNK463, an orally bioavailable pan-WNK kinase inhibitor that exploits unique structural properties of the WNK catalytic domain to achieve high affinity and kinase selectivity, illustrates a strategy of leveraging distinct kinase features to develop specific inhibitors and validates the genetic predictions of the in vivo pharmacology of WNK inhibition.

Original languageEnglish
Article numberpe3
Pages (from-to)1-3
Number of pages4
JournalScience Signaling
Volume9
Issue number450
DOIs
Publication statusPublished - 18 Oct 2016

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