WNK463 |
Katalog-Nr.GC19383
One-Click Copy Product Info
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WNK463 hemmt die pan-With-No-Lysine (K) (WNK)-Kinase und zeigt IC50-Werte von 5 nM, 1 nM, 5 nM bzw. 9 nM für WNK1, WNK2, WNK3 und WNK4.
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 hemmt die pan-With-No-Lysine (K) (WNK)-Kinase und zeigt IC50-Werte von 5 nM, 1 nM, 5 nM bzw. 9 nM für WNK1, WNK2, WNK3 und WNK4[1-2].
WNK463 bei 1 μM für 15 Minuten verringerte die KCC2-Phosphorylierung an Stelle 1007 und erhöhte die KCC2-Aktivität in HEK-293-Zellen[3]. WNK463(10 μM ;2 Stunden) signifkant erhöhte die p38-Aktivierung in HeLa-Zellen[4]. Die Hemmung von WNK1 durch WNK463(10 μM) führt zu einem Ca2+-Einstrom und einer Permeabilität im Lungenendothel über das transiente Rezeptorpotenzial Vanilloid[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.
| Zellexperiment [1]: | |
Zelllinien | HEK-293 Zellen |
Vorbereitungsmethode | Zellen, die mit hKCC2-cDNA-Ülasmiden transfiziert wurden, wurden 3 Tage nach der Transfektion entweder mit WNK463 (1 μM) oder DMSO (0.1%) für 15 Minuten bei 37 ℃ behandelt. |
Reaktionsbedingungen | 1 μM; 15 Minuten |
Anwendungen | WNK463 verringerte die Phosphorylierung des K+/Cl- Cotransportes 2 (KCC2) und erhöhte die KCC2-Aktivität in HEK-293-Zellen. |
| Tierversuch [1]: | |
Tiermodelle | C57BL/6 männliche Mäuse(Alzet-Pumpenimplantationsoperationen) |
Vorbereitungsmethode | Die Mini-Osmosepumpen wurden mit 100 μl WNK463 (8.57 mM) oder DMSO (14.2%) beladen und an das Gehirninfusionskit angeschlossen. Die Geschwindifkeit der Wirtstoffabgabe durch die osmotischen Alzet-Pumpen betrug 0,25 µl/Stunde, was zu Endkonzentrationen von 60 µM WNK463 und 0,1% DMSO im Gehirn führte. |
Dosierungsform | 100 μl WNK463 (8.57 mM) (0.857μmol); intrahippocampusale Infusion;7 Tage |
Anwendungen | WNK463 reduziert die KCC2-Phosphorylierung in vivo. |
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. | |
| 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 |
| Löslichkeit | 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 | |||
|
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
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.)
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.)