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WNK463 Serine/threonin kinase inhibitor

Name: WNK463
Brand: Selleck Chemicals
SKU: S8358
Availability: InStock
Rating: 5 (16 reviews)

Cat.No.S8358

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.

Chemical Structure

Molecular Weight: 463.46

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Quality Control

Batch: Purity: 99.76%

99.76

Related Targets	Bcl-2 Caspase PD-1/PD-L1 Ferroptosis p53 Apoptosis related Synthetic Lethality STAT TNF-alpha Ras
Other Serine/threonin kinase Inhibitors	GCN2iB SRPIN340 Benzamidine HCl SPHINX31 BAY-1816032 ML281 DCLK1-IN-1 SGC-GAK-1 WNK-IN-11 MKI-1

Solubility

In vitro
Batch:

DMSO : 92 mg/mL (198.5 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 92 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 30%PEG300 2 5%Tween80 3 60%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	8.000mg/ml (17.26mM)	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.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

% Tween 80

% ddH₂O

% DMSO

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	463.46	Formula	C₂₁H₂₄F₃N₇O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	2012607-27-9	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC(C)(C)NC(=O)C1=CN=CN1C2CCN(CC2)C3=NC=C(C=C3)C4=NN=C(O4)C(F)(F)F

Mechanism of Action

Targets/IC₅₀/Ki	WNK2 1nM WNK1 5nM WNK3 6nM WNK4 9nM
In vitro	WNK463 potently inhibited the in vitro kinase activity of all four WNK family members (WNK1, WNK2, WNK3, and WNK4). This compound 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.
In vivo	In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electrolyte homeostasis. This compound 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), this compound 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, this chemical produced significant and dose-dependent increases in urine output as well as urinary sodium and potassium excretion rates. Orally administered this compound also significantly decreased blood pressure in these hypertensive mice. It elicited in vivo cardiovascular and renal effects through WNK kinase inhibition.
References	[1] https://pubmed.ncbi.nlm.nih.gov/27595330/ [2] https://pubmed.ncbi.nlm.nih.gov/35867836/

Applications

Methods	Biomarkers	Images	PMID
Western blot	pSPAK/pOSR1		31207112

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Handling Instructions

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