WNK463

Catalog No.S8358 Batch:S835802

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Technical Data

Formula

C21H24F3N7O2
Molecular Weight 463.46 CAS No. 2012607-27-9
Solubility (25°C)* In vitro DMSO 92 mg/mL (198.5 mM)
Ethanol 92 mg/mL (198.5 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 30%PEG300 5%Tween80 60%ddH2O
8.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 160 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 600 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description WNK463 is a pan-WNK-kinase inhibitor. It potently inhibits the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4) with IC50 of 5nM, 1nM, 6nM, and 9nM.
Targets
WNK2 [1] WNK1 [1] WNK3 [1] WNK4 [1]
1nM 5nM 6nM 9nM
In vitro

WNK463 potently inhibited the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4). WNK463 also inhibited WNK1-catalyzed phosphorylation of the native WNK substrate, oxidative stress response 1 (OSR1) in a biochemical assay and in human embryonic kidney 293 (HEK293) cells that express exogenous OSR1 and that are activated by sorbitol-mediated osmotic stress[1].
In vivo

In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electrolyte homeostasis. WNK463 is orally bioavailable in C57BL/6 mice (100%) and Sprague Dawley rats (74%), with a half-life of 3.6 and 2.1 h, respectively. In spontaneously hypertensive rats (SHRs), WNK463 administered orally (p.o.) at 1, 3, or 10 mg per kg body weight (mg/kg) p.o. achieved maximum plasma concentration (Cmax) values of 88, 441, and 1,170 nM, respectively. These exposures produced dose-dependent decreases in blood pressure and simultaneous increases in heart rate in conscious SHRs. Moreover, WNK463 produced significant and dose-dependent increases in urine output as well as urinary sodium and potassium excretion rates. Orally administered WNK463 also significantly decreased blood pressure in these hypertensive mice. WNK463 elicited in vivo cardiovascular and renal effects through WNK kinase inhibition[1].

Protocol (from reference)

Cell Assay:

[2]
  • Cell lines

    HUVECs

  • Concentrations

    1 µM

  • Incubation Time

    6 h

  • Method

    Cells were treated with indicated concentration of drug for 6 h.
Animal Study:

[1]
  • Animal Models

    Male Sprague Dawley rats or male C57BL/6 mice

  • Dosages

    1 mg/kg(i.v.) or 3 mg/kg (oral)

  • Administration

    i.v. or oral administration

Selleck's WNK463 has been cited by 14 publications

Identification and In Vivo Validation of Unique Anti-Oncogenic Mechanisms Involving Protein Kinase Signaling and Autophagy Mediated by the Investigational Agent PV-10 [ Cancers (Basel), 2024, 16(8)1520] PubMed: 38672602
Isoform-independent promotion of contractility and proliferation, and suppression of survival by with no lysine/K kinases in prostate stromal cells [ FASEB J, 2024, 38(7):e23604] PubMed: 38591106
WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling [ bioRxiv, 2024, 2024.06.09.598125] PubMed: 38915673
The WNK1-ERK5 route plays a pathophysiological role in ovarian cancer and limits therapeutic efficacy of trametinib [ Clin Transl Med, 2023, 13(4):e1217] PubMed: 37029785
The WNK1-ERK5 route plays a pathophysiological role in ovarian cancer and limits therapeutic efficacy of trametinib [ Clin Transl Med, 2023, 13(4):e1217] PubMed: 37029785
WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis [ Proc Natl Acad Sci U S A, 2022, 119(30):e2203743119] PubMed: 35867836
Cancer genes disfavoring T cell immunity identified via integrated systems approach [ Cell Rep, 2022, 40(5):111153] PubMed: 35926468
WNK Inhibition Increases Surface Liquid pH and Host Defense in Cystic Fibrosis Airway Epithelia [ Am J Respir Cell Mol Biol, 2022, 67(4):491-502] PubMed: 35849656
Discovery of Small Molecule KCC2 Potentiators Which Attenuate In Vitro Seizure-Like Activity in Cultured Neurons [ Front Cell Dev Biol, 2022, 10:912812] PubMed: 35813195
WNK1 Enhances Migration and Invasion in Breast Cancer Models [ Mol Cancer Ther, 2021, 20(10):1800-1808] PubMed: 34253593

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.