Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.

ABSTRACT:

Introduction

WNK [with no lysine (K)] kinases are serine/threonine kinases associated with familial hyperkalemic hypertension (FHHt). WNKs are therapeutic targets for blood pressure regulation, stroke and several cancers including triple negative breast cancer and glioblastoma. Here, we searched for and characterized novel WNK kinase inhibitors.

Methods

We used a ~210,000-compound library in a high-throughput screen, re-acquisition and assay, commercial specificity screens and crystallography to identify WNK-isoform-selective inhibitors.

Results

We identified five classes of compounds that inhibit the kinase activity of WNK1: quinoline compounds, halo-sulfones, cyclopropane-containing thiazoles, piperazine-containing compounds, and nitrophenol-derived compounds. The c

SUBMITTER: Chlebowicz J 

PROVIDER: S-EPMC9880028 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature