WNK463 |
| رقم الكتالوجGC19383 |
WNK463 هو مثبط متاح حيويًا شفوياً مع عدم وجود ليسين (K) (WNK) - كيناز مع IC50s من 5 نانومتر ، 1 نانومتر ، 6 نانومتر ، و 9 نانومتر لـ WNK1 ، WNK2 ، WNK3 ، و WNK4 ، على التوالي
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 |
| الذوبان | 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 | 0.4315 mL | 2.1577 mL | 4.3154 mL |
| 10 mM | 0.2158 mL | 1.0788 mL | 2.1577 mL |
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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.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)
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