Journal
NATURE CHEMICAL BIOLOGY
Volume 12, Issue 11, Pages 896-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEMBIO.2168
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Funding
- DOE Office of Science by Argonne National Laboratory [DE-AC02-06CH11357]
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The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. Herein, we introduce the first orally bioavailable pan-WNK-kinase inhibitor, WNK463, that exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electrolyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.
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