WNK463 |
Catalog No.GC19383
One-Click Copy Product Info
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WNK463 inhibits the pan-With-No-Lysine (K) (WNK) kinase, demonstrating IC50 values of 5 nM, 1 nM, 6 nM, and 9 nM for WNK1, WNK2, WNK3, and WNK4, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2012607-27-9
Sample solution is provided at 25 µL, 10mM.
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WNK463 inhibits the pan-With-No-Lysine (K) (WNK) kinase, demonstrating IC50 values of 5 nM, 1 nM, 6 nM, and 9 nM for WNK1, WNK2, WNK3, and WNK4, respectively[1-2].
WNK463 at 1 μM for 15 minutes decreased KCC2 phosphorylation at site 1007 and increased KCC2 activity in HEK-293 cells[3]. WNK463(10 μM ;2h) significantly enhanced p38 activation in HeLa cells[4]. Inhibition of WNK1 by WNK463(10 μM) leads to Ca2+ influx and permeability in lung endothelium via transient receptor potential vanilloid 4[5].
WNK blockade by WNK463 (1 mg/kg; oral in water;3days) decreases TRPV4 activity and expression in the aldosterone-sensitive distal nephron (ASDN) in mice[6]. WNK463 (8.57 mM, 100 μl, 0.857 μmol) administered via intra-hippocampal infusion for 7 days reduces KCC2-T1007 phosphorylation and restricts kainite (KA)-induced status epilepticus in vivo[3]. WNK1–OSR1 axis inhibitors WNK463(11μM,5μL; p.o; twice a week for a month) combined with oligo-fucoidan attenuate hepatocellular carcinoma (HCC) proliferation[7].
References:
[1]. Yamada K, Park HM, et,al. Small-molecule WNK inhibition regulates cardiovascular and renal function. Nat Chem Biol. 2016 Nov;12(11):896-898. doi: 10.1038/nchembio.2168. Epub 2016 Sep 5. PMID: 27595330.
[2]. Jonniya NA, Kar P. Investigating specificity of the anti-hypertensive inhibitor WNK463 against With-No-Lysine kinase family isoforms via multiscale simulations. J Biomol Struct Dyn. 2020 Mar;38(5):1306-1321. doi: 10.1080/07391102.2019.1602079. Epub 2019 Apr 24. PMID: 31017050.
[3]. Lee KL, Abiraman K, et,al. Inhibiting with-no-lysine kinases enhances K+/Cl- cotransporter 2 activity and limits status epilepticus. Brain. 2022 Apr 29;145(3):950-963. doi: 10.1093/brain/awab343. PMID: 34528073; PMCID: PMC9050525.
[4]. Liu Z, Demian W, et,al. Regulation of the p38-MAPK pathway by hyperosmolarity and by WNK kinases. Sci Rep. 2022 Aug 25;12(1):14480. doi: 10.1038/s41598-022-18630-w. PMID: 36008477; PMCID: PMC9411163.
[5]. Erfinanda L, Zou L, et,al. Loss of endothelial CFTR drives barrier failure and edema formation in lung infection and can be targeted by CFTR potentiation. Sci Transl Med. 2022 Dec 7;14(674):eabg8577. doi: 10.1126/scitranslmed.abg8577. Epub 2022 Dec 7. PMID: 36475904.
[6]. Tomilin VN, Pyrshev K, et,al. With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron. Cells. 2021 Jun 12;10(6):1482. doi: 10.3390/cells10061482. PMID: 34204757; PMCID: PMC8231605.
[7]. Hou CY, Ma CY, et,al. WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy. Int J Mol Sci. 2022 Oct 11;23(20):12100. doi: 10.3390/ijms232012100. PMID: 36292952; PMCID: PMC9602556.
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Cell experiment [1]: |
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Cell lines |
HEK-293 cells |
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Preparation method |
Cells transfected with hKCC2 cDNA plasmids were treated with either WNK463 (1 μM) or DMSO (0.1%) for 15 minutes at 37℃, three days post-transfection. |
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Reaction Conditions |
1 μM; 15 min |
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Applications |
WNK463 decreased K+/Cl- cotransporter 2 (KCC2) phosphorylation and increased KCC2 activity in HEK-293 cells. |
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Animal experiment [1]: |
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Animal models |
C57BL/6 male mice (Alzet pump implantation surgeries) |
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Preparation method |
Mini-osmotic pumps were loaded with 100 μl WNK463 (8.57 mM) or DMSO (14.2%) and connected to brain infusion kit. The rate of drug delivery by the Alzet osmotic pumps was 0.25 µl/h, resulting in final concentrations of 60 µM WNK463 and 0.1% DMSO in the brain. |
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Dosage form |
100 μl WNK463 (8.57 mM) (0.857μmol); intra hippocampal infusion;7days |
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Applications |
WNK463 reduces KCC2 phosphorylation in vivo. |
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References: [1]. Lee KL, Abiraman K, et,al. Inhibiting with-no-lysine kinases enhances K+/Cl- cotransporter 2 activity and limits status epilepticus. Brain. 2022 Apr 29;145(3):950-963. doi: 10.1093/brain/awab343. PMID: 34528073; PMCID: PMC9050525. |
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| Cas No. | 2012607-27-9 | SDF | |
| Canonical SMILES | FC(F)(F)C1=NN=C(O1)C2=CN=C(N3CCC(N4C=NC=C4C(NC(C)(C)C)=O)CC3)C=C2 | ||
| Formula | C21H24F3N7O2 | M.Wt | 463.46 |
| Solubility | DMSO : ≥ 30 mg/mL (64.73 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1577 mL | 10.7884 mL | 21.5768 mL |
| 5 mM | 431.5 μL | 2.1577 mL | 4.3154 mL |
| 10 mM | 215.8 μL | 1.0788 mL | 2.1577 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)