| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
WNK463 (NVP-WNK463) is a novel, potent and orally bioavailable pan-WNK-kinase inhibitor with IC50s of 5, 1, 6, and 9 nM for WNK1, WNK 2, WNK 3, and WNK 4, respectively. The With-No-Lysine (K) (WNK) kinases play a critical role in blood pressure regulation and body fluid and electrolyte homeostasis. WNK463 exploits unique structural features of the WNK kinases for both affinity and kinase selectivity. In rodent models of hypertension, WNK463 affects blood pressure and body fluid and electro-lyte homeostasis, consistent with WNK-kinase-associated physiology and pathophysiology.
| ln Vitro |
The phosphorylation of the WNK1 downstream target SPAK/OSR1 in human tissue engineered hierarchy (hTEC) is decreased by WNK463 treatment (50 nM, 1 μM, 10 μM; 6 days) [1].
|
|---|---|
| ln Vivo |
In conscious SHR, administration with WNK463 (1–10 mg/kg; final product; 4 hours; autohypertensive Sprague Dawley status) resulted in a dose-dependent drop in blood glucose and an increase in heart rate concurrently. Urinary sodium WNK463 is internally generated in Sprague Dawley and is bioavailable internally in urine output, with a half-life of 2.1 hours [1].
|
| Cell Assay |
Western Blot Analysis[2]
Cell Types: Human tissue engineered cornea (hTEC) Tested Concentrations: 50 nM, 1 μM, 10 μM Incubation Duration: 6 days Experimental Results: The phosphorylation of WNK1 downstream target SPAK/OSR1 was diminished in injured hTEC. |
| Animal Protocol |
Animal/Disease Models: Spontaneously hypertensive Sprague Dawley rats (34-42 weeks old)) [1]
Doses: 1 mg/kg, 3 mg/kg or 10 mg/kg (pharmacokinetic/PK/PK studies) Route of Administration: Oral ; 4-hour Experimental Results: blood pressure dropped and heart rate increased at the same time. WNK463 Dramatically and dose-dependently increased urine output and urinary sodium and potassium excretion rates. |
| References |
[1]. Yamada K et al. Small-molecule WNK inhibition regulates cardiovascular and renal function. Nat Chem Biol. 2016 Nov;12(11):896-898.
[2]. Desjardins P, et al. Contribution of the WNK1 kinase to corneal wound healing using the tissue-engineered human cornea as an in vitro model. J Tissue Eng Regen Med. 2019 Sep;13(9):1595-1608. |
| Molecular Formula |
C21H24F3N7O2
|
|---|---|
| Molecular Weight |
463.4562
|
| CAS # |
2012607-27-9
|
| SMILES |
O=C(C1=CN=CN1C2CCN(C3=NC=C(C4=NN=C(C(F)(F)F)O4)C=C3)CC2)NC(C)(C)C
|
| InChi Key |
HWSHOMMVLGBIDN-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H24F3N7O2/c1-20(2,3)27-17(32)15-11-25-12-31(15)14-6-8-30(9-7-14)16-5-4-13(10-26-16)18-28-29-19(33-18)21(22,23)24/h4-5,10-12,14H,6-9H2,1-3H3,(H,27,32)
|
| Chemical Name |
N-tert-Butyl-3-[1-[5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]piperidin-4-yl]imidazole-4-carboxamide
|
| Synonyms |
NVP-WNK463; NVP-WNK 463; NVP-WNK-463; WNK463; WNK-463; WNK 463.
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 30 mg/mL (~64.73 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA