Small-molecule WNK inhibition regulates cardiovascular and renal function.

Abstract:

: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 electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Yamada K,Park HM,Rigel DF,DiPetrillo K,Whalen EJ,Anisowicz A,Beil M,Berstler J,Brocklehurst CE,Burdick DA,Caplan SL,Capparelli MP,Chen G,Chen W,Dale B,Deng L,Fu F,Hamamatsu N,Harasaki K,Herr T,Hoffmann P,Hu QY,

doi

10.1038/nchembio.2168

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

896-898

issue

11

eissn

1552-4450

issn

1552-4469

pii

nchembio.2168

journal_volume

12

pub_type

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