WNK2-IN-1
Based on 1 Customer Validation
WNK2-IN-1 is a WNK2 inhibitor. WNK2-IN-1 inhibits the kinase activity of recombinant WNK2 in a dose-dependent manner, and simultaneously partially inhibits WNK3 and WNK4. WNK2-IN-1 modulates WNK2-SPAK downstream signaling by inhibiting WNK2-mediated SPAK phosphorylation, and further suppresses the proinflammatory transcriptional response induced by IL1β. WNK2-IN-1 can be used in studies related to the WNK2 signaling pathway and osteoarthritis.
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- Purity : 96.85%
- CAS No.: 2728520-90-7
- 화학식: C19H20F6N4O
- 분자량:434.38
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보관:
Store at room temperature, keep dry and cool.
In solvent -80°C, 1 year , -20°C, 6 months
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
WNK2 |
WNK3 |
WNK4 |
In Vitro
WNK2-IN-1 (1-400 μM) reduces pSPAK levels in T/C-28a2 chondrocytes in a dose-dependent manner; at 200-400 μM, its reducing effect on pSPAK is comparable to that of the pan-WNK inhibitor WNK463 (HY-100626)[1].
WNK2-IN-1 (1-200 μM) reduces WNK2 kinase activity in a dose-dependent manner in recombinant kinase assays; it does not affect WNK1 under the same conditions, and decreases WNK3 and WNK4 activity in a dose-dependent manner. However, the degree of inhibition of WNK3/WNK4 is weaker than that of WNK2, and does not reach the inhibitory level of WNK463[1].
WNK2-IN-1 (400 μM; 5 min) reduces pSPAK to levels comparable to those achieved with WNK463 in T/C-28a2 chondrocytes; (R)-WNK2-IN-1 produces a similar reduction in pSPAK, whereas (S)-WNK2-IN-1 exhibits only a minor effect, indicating that the R-enantiomer is the active form[1].
Compared with WNK463 (10 μM), WNK2-IN-1 (100 μM; 24 h) upregulates MMP2 and MMP13 and downregulates GREM2 and BMP4 in primary human chondrocytes not stimulated with IL1β; meanwhile, it enhances cell growth, Hedgehog signaling pathway inhibition, and immune response-related pathways, and downregulates autophagy-, starvation response-, and chemical stress-related pathways[1].
WNK2-IN-1 (100 μM; 24 h; 10 ng/mL IL1β; 100 mM Sorbitol) reduces the expression of CCL2 and FGF1 in primary human chondrocytes; no significant changes in gene expression are observed in control chondrocytes not stimulated with IL1β[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:human T/C-28a2 chondrocytes
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Concentration:0.1-1000 μM
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Incubation Time:24 h (before adding XTT); 4 h (additional incubation with XTT working solution)
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Result:Exhibited very low cytotoxicity in human T/C-28a2 chondrocytes, with a cell viability IC50 value of 416 μM.
Showed an IC50 value substantially higher than the cytotoxic IC50 values of other screened candidate WNK2 inhibitors, indicating excellent tolerability.
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Cell Line:human T/C-28a2 chondrocytes
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Concentration:1, 10, 50, 100, 200, 400 μM
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Incubation Time:15 min (pre-exposure before media replacement); 10 min (further incubation under isotonic or hyperosmotic 500 mOsm conditions prior to cell harvest)
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Result:Produced a dose-dependent reduction in pSPAK levels under both isotonic (300 mOsm) and acute 500 mOsm osmotic stress conditions.
Reduced pSPAK accumulation to levels comparable to the pan-WNK control inhibitor at 200 μM and 400 μM, confirming effective inhibition of WNK2-mediated SPAK phosphorylation.
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Cell Line:human T/C-28a2 chondrocytes
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Concentration:400 μM (racemic WNK2-IN-1 (M04)); 400 μM ((R)-M04); 400 μM ((S)-M04)
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Incubation Time:5 min (incubation under 500 mOsm osmotic stress)
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Result:Reduced pSPAK levels to an extent comparable to the control pan-WNK inhibitor when using 400 μM racemic WNK2-IN-1 (M04) or 400 μM (R)-M04.
Produced only a minor inhibitory effect on pSPAK accumulation when using 400 μM (S)-M04.
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Cell Line:human T/C-28a2 chondrocytes
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Concentration:100 μM
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Incubation Time:24 h (during 10 ng/mL IL1β stimulation in 100 mM Sorbitol hyperosmotic media)
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Result:Reduced the elevated expression of proinflammatory genes IL6 and CCL2 back to near non-stimulated control levels in IL1β-stimulated T/C-28a2 chondrocytes.
Increased the expression of the cartilage anabolic collagen gene COL2A1, and prevented the IL1β-induced downregulation of the key cartilage proteoglycan gene ACAN.
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Cell Line:primary human articular chondrocytes
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Concentration:100 μM
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Incubation Time:24 h (during 10 ng/mL IL1β stimulation in 100 mM Sorbitol hyperosmotic media)
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Result:Significantly reduced the IL1β-induced upregulation of the proinflammatory genes CCL2 and FGF1 in IL1β-stimulated primary human chondrocytes.
Did not induce any significant changes in baseline gene expression in non-IL1β-stimulated control chondrocytes.
Chemical Information
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CAS No. 2728520-90-7
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Appearance Solid
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분자량 434.38
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화학식 C19H20F6N4O
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Color Off-white to yellow
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SMILES
OCC1N(C2=NC=NC(N(CC3=CC(C(F)(F)F)=CC(C(F)(F)F)=C3)C)=C2)CCC1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Store at room temperature, keep dry and cool
In solvent -80°C 1 year -20°C 6 months
용액&용해도
In Vitro:
DMSO : 100 mg/mL (230.21 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
순도&문서
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Data Sheet (288 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3021 mL | 11.5107 mL | 23.0213 mL | 57.5533 mL |
| 5 mM | 0.4604 mL | 2.3021 mL | 4.6043 mL | 11.5107 mL | |
| 10 mM | 0.2302 mL | 1.1511 mL | 2.3021 mL | 5.7553 mL | |
| 15 mM | 0.1535 mL | 0.7674 mL | 1.5348 mL | 3.8369 mL | |
| 20 mM | 0.1151 mL | 0.5755 mL | 1.1511 mL | 2.8777 mL | |
| 25 mM | 0.0921 mL | 0.4604 mL | 0.9209 mL | 2.3021 mL | |
| 30 mM | 0.0767 mL | 0.3837 mL | 0.7674 mL | 1.9184 mL | |
| 40 mM | 0.0576 mL | 0.2878 mL | 0.5755 mL | 1.4388 mL | |
| 50 mM | 0.0460 mL | 0.2302 mL | 0.4604 mL | 1.1511 mL | |
| 60 mM | 0.0384 mL | 0.1918 mL | 0.3837 mL | 0.9592 mL | |
| 80 mM | 0.0288 mL | 0.1439 mL | 0.2878 mL | 0.7194 mL | |
| 100 mM | 0.0230 mL | 0.1151 mL | 0.2302 mL | 0.5755 mL |
WNK2-IN-1 Related Classifications
HY-189224 Related Classifications
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Keywords
- WNK2-IN-1
- 2728520-90-7
- Ser/Thr Kinase
- WNK Kinase
- Protein Serine-Threonine Kinase
- With-no-lysine (WNK) kinase
- osteoarthritis
- SPAK phosphorylation
- WNK2 kinase domain
- chondrocytes
- molecular dynamics simulation
- WNK2 kinase
- primary human articular chondrocytes
- blood-brain barrier
- WNK pathway
- human T/C-28a2 chondrocytes
- Inhibitor
- inhibitor
- inhibit