| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
WNK-IN-12 targets the WNK1 kinase, a member of the WNK family of serine/threonine protein kinases. These kinases play a crucial role in regulating ion transport, cell volume, and blood pressure. The compound binds to the ATP-binding site of WNK kinases, preventing the phosphorylation of downstream targets.
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| ln Vitro |
In vitro, WNK-IN-12 is a potent inhibitor of WNK1 kinase activity. Its inhibitory effects are demonstrated in biochemical assays measuring the phosphorylation of WNK substrates. The compound's potency and selectivity are key features of its in vitro profile.
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| ln Vivo |
WNK-IN-11 D3 (1.5 mg/kg; oral) revealed better rat PK parameters, including lower clearance, improved absolute oral exposure, and a 2-fold improvement in oral bioavailability [1]. WNK-IN-11 D3 (30 mg/kg; oral) exhibited a significant drop in systolic blood pressure (SBP) compared to untreated animals [1]. WNK-IN-11 D3 (0~100 mg/kg; oral) produces dose-dependent diuresis, natriuresis, and potassium excretion in the range of 10 to 100 mg/kg [1]. WNK-IN-11 D3 exhibited a trend toward lower blood pressure, stroke volume, and total peripheral resistance, while increased heart rate. WNK-IN-11 D3 has showed effectiveness in rodent models of hypertension and volume overload [1].
In vivo, WNK-IN-12 is an orally active compound. By inhibiting WNK kinases, it effectively regulates cardiovascular homeostasis, leading to effects such as lowered blood pressure, reduced stroke volume, and decreased total peripheral resistance, while increasing heart rate. |
| Enzyme Assay |
The inhibitory activity of WNK-IN-12 is determined using standard kinase assays. These cell-free assays measure the compound's ability to inhibit the phosphorylation activity of purified WNK1 kinase, often using a specific peptide substrate and quantifying the remaining kinase activity.
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| Cell Assay |
Cell-based assays are used to confirm the compound's mechanism of action. These involve treating cells with WNK-IN-12 and measuring the phosphorylation levels of downstream targets of WNK kinases, such as SPAK and OSR1, to demonstrate target engagement and pathway inhibition.
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| Animal Protocol |
Animal/Disease Models: SD (SD (Sprague-Dawley)) rat[1]
Doses: 1.5 mg/kg Route of Administration: Oral Experimental Results: Improved rat PK profile, including diminished clearance, improved absolute oral exposure, and 2-fold increase in oral bioavailability . Animal/Disease Models: FVB mice [1] Doses: 30 mg/kg Route of Administration: Oral Experimental Results: Systolic blood pressure (SBP) was Dramatically diminished compared to untreated mice. Animal/Disease Models: FVB mice [1] Doses: 0~100 mg/kg Route of Administration: Po Experimental Results: 10 to 100 mg/kg induces dose-dependent diuresis, natriuresis and potassiumuria. The in vivo efficacy of WNK-IN-12 is evaluated in animal models of hypertension. Rodent models are typically used to measure the compound's effect on blood pressure and other cardiovascular parameters following oral administration, as described in its profile. |
| ADME/Pharmacokinetics |
WNK-IN-12 is an orally active compound. Its pharmacokinetic properties, such as oral bioavailability, half-life, and tissue distribution, would be characteristic of a small molecule designed for oral administration. Specific PK parameters are not detailed in the available literature.
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| Toxicity/Toxicokinetics |
Specific toxicity data for WNK-IN-12 is not provided. As a kinase inhibitor, its safety profile would be a critical aspect of its development. Standard toxicological studies would be required to assess its safety for potential therapeutic applications.
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| References | |
| Additional Infomation |
WNK-IN-12 is a research tool for studying the biological functions of WNK kinases. Its development as an orally active inhibitor highlights the therapeutic potential of targeting the WNK kinase pathway for the treatment of hypertension and other diseases involving dysregulated ion transport, such as cancer.
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| Molecular Formula |
C21H21CL2N5OS
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|---|---|
| Molecular Weight |
462.395340681076
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| Exact Mass |
464.103
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| CAS # |
2123483-49-6
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| Related CAS # |
WNK-IN-11;2123489-30-3
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| PubChem CID |
137660903
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
572
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(N1CCN(CC2C=CC(Cl)=CC=2)CC1)(C1=C(C=NC(C2=CSC(NC([H])([H])[H])=N2)=C1)Cl)=O
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| InChi Key |
MVXAYIXYYOVALX-FIBGUPNXSA-N
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| InChi Code |
InChI=1S/C21H21Cl2N5OS/c1-24-21-26-19(13-30-21)18-10-16(17(23)11-25-18)20(29)28-8-6-27(7-9-28)12-14-2-4-15(22)5-3-14/h2-5,10-11,13H,6-9,12H2,1H3,(H,24,26)/i1D3
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| Chemical Name |
[4-[(4-chlorophenyl)methyl]piperazin-1-yl]-[5-chloro-2-[2-(trideuteriomethylamino)-1,3-thiazol-4-yl]pyridin-4-yl]methanone
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~214.86 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1626 mL | 10.8131 mL | 21.6263 mL | |
| 5 mM | 0.4325 mL | 2.1626 mL | 4.3253 mL | |
| 10 mM | 0.2163 mL | 1.0813 mL | 2.1626 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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