Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition

TY - JOUR

T1 - Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition

AU - Zhang, Jinwei

AU - Deng, Xianming

AU - Kahle, Kristopher T.

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

U2 - 10.1126/scisignal.aaj2227

DO - 10.1126/scisignal.aaj2227

M3 - Review article

C2 - 27811182

AN - SCOPUS:84991786815

SN - 1945-0877

VL - 9

SP - 1

EP - 3

JO - Science Signaling

JF - Science Signaling

IS - 450

M1 - pe3

ER -