VU591
Based on 1 Customer Validation
VU591 is a selective inhibitor of the renal outer medullary potassium channel (ROMK, Kir1.1). VU591 inhibits ROMK via binding to the intracellular pore region near residues Val168 and Asn171, with IC50 of 240 nM in Tl+ flux assay and 300 nM in whole cell patch clamp electrophysiology, suppresses native ROMK mediated K+ secretion in isolated perfused rat collecting ducts, and exerts antidepressive effects in the mouse tail suspension test (TST). VU591 can be used for the study of ROMK channel function, renal potassium handling, antidepressant mechanisms, and diuretic drug discovery.
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- Pureza: 98.81%
- No. CAS: 1222810-74-3
- Fòrmula: C16H12N6O5
- Peso molecular:368.30
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Almacenamiento:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
IC50: 0.24 μM (ROMK)[1].
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
0.24 μM
Compound: 2
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Inhibition of ROMK S44D mutant expressed in HEK293 cells assessed as inhibition of thallium efflux incubated for 20 mins prior to thallium addition measured after 7 to 12 secs by fluorescence assay.
Inhibition of ROMK S44D mutant expressed in HEK293 cells assessed as inhibition of thallium efflux incubated for 20 mins prior to thallium addition measured after 7 to 12 secs by fluorescence assay.
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24900480 |
| HEK293 | IC50 |
240 nM
Compound: 3; VU591
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Inhibition of rat ROMK1 expressed in HEK293 cells by Tl+ flux assay.
Inhibition of rat ROMK1 expressed in HEK293 cells by Tl+ flux assay.
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31034224 |
VU591 (1 nM-30 μM; 5-10 min) inhibits rat ROMK1 (Kir1.1) with IC50 of 240 nM in Tl+ flux assay and 300 nM in whole-cell patch-clamp electrophysiology[1].
VU591 (10 μM; 4 10 min) produces 86% inhibition of human ROMK1 in patch clamp assay, and shows no significant inhibition of Kir7.1, Kir2.1, Kir2.3, Kir4.1, Kir6.2/SUR1, Slo1/β1, Kv1.3, or hERG channels[1].
VU591 (1-10 μM; luminal perfusion) inhibits net K+ transport (JK) from 7.0 to 3.6 pmol/min/mm in isolated perfused rat cortical collecting ducts, with no significant effect on Na+ transport[1].
VU591 (300 nM) shows voltage-dependent "knock-off" at hyperpolarizing potentials, with block decreasing at strong negative voltages[1].
VU591 (10 μM; 4 h dialysis) exhibits high plasma protein binding (human: 99.14%; rat: 98.39%) in rapid equilibrium dialysis assay[1].
VU591 (15 min incubation) shows metabolic stability, with 60-80% compound remaining in human and rat liver microsomes[1].
VU591 (up to 30 μM) inhibition of ROMK is abolished by mutation of pore residues Val168 and Asn171[3].
VU591 (50 and 100 μM; 4-10 min) exhibits 6.8% and 22.6% inhibition for Kir2.1 D172N, and 9% and 28% inhibition for Kir2.1 C169V/D172N at corresponding concentrations[3].
VU591 (20 μM; 20 min) blocks the cardioprotective effect of diazoxide in isolated mouse cardiomyocytes[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HEK-293 cells stably expressing ROMK-S44D (C1 cells)
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Concentration:1, 3, 10, 30, 100, 300 nM; 1, 3, 10, 30 μM
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Incubation Time:Approximately 20 min (pre-incubation) + 5-12 s (Tl+ addition)
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Result:Inhibited ROMK with IC50 of 240 nM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice (6 weeks old, male)[2]
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Dosage:5 μL of 20 mM
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Administration:i.c.v.; single injection; 30 min before behavioral testing
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Result:Decreased immobile time in the tail suspension test (TST), confirming ROMK involvement in antidepressant-like effects.
Chemical Information
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No. CAS 1222810-74-3
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Appearance Solid
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Peso molecular 368.30
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Fòrmula C16H12N6O5
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Color Light yellow to yellow
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SMILES
O=[N+]([O-])C1=CC(NC(COCC2=NC3=C(N2)C=C([N+]([O-])=O)C=C3)=N4)=C4C=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Solvente y solubilidad
DMSO : 62.5 mg/mL (169.70 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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.65 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Pureza y Documentación
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Ficha de datos (276 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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Instrucciones de manejo (2659 KB)
Referencias
[1]. Bhave G, et al. Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel. Mol Pharmacol. 2011 Jan;79(1):42-50. [Content Brief]
[2]. Okada M, et al. Antidepressive effect of an inward rectifier K+ channel blocker peptide, tertiapin-RQ. PLoS One. 2020 Nov 13;15(11):e0233815. [Content Brief]
[3]. Swale DR, et al. Computational and functional analyses of a small-molecule binding site in ROMK. Biophys J. 2015 Mar 10;108(5):1094-103. [Content Brief]
[4]. Sammons MF, et al. Discovery and in Vitro Optimization of 3-Sulfamoylbenzamides as ROMK Inhibitors. ACS Med Chem Lett. 2018 Jan 19;9(2):125-130. [Content Brief]
[5]. Wang J, et al. Kir1.1 and SUR1 are not implicated as subunits of an adenosine triphosphate-sensitive potassium channel involved in diazoxide cardioprotection. JTCVS Open. 2023 Jun 16;15:231-241. [Content Brief]
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, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7152 mL | 13.5759 mL | 27.1518 mL | 67.8794 mL |
| 5 mM | 0.5430 mL | 2.7152 mL | 5.4304 mL | 13.5759 mL | |
| 10 mM | 0.2715 mL | 1.3576 mL | 2.7152 mL | 6.7879 mL | |
| 15 mM | 0.1810 mL | 0.9051 mL | 1.8101 mL | 4.5253 mL | |
| 20 mM | 0.1358 mL | 0.6788 mL | 1.3576 mL | 3.3940 mL | |
| 25 mM | 0.1086 mL | 0.5430 mL | 1.0861 mL | 2.7152 mL | |
| 30 mM | 0.0905 mL | 0.4525 mL | 0.9051 mL | 2.2626 mL | |
| 40 mM | 0.0679 mL | 0.3394 mL | 0.6788 mL | 1.6970 mL | |
| 50 mM | 0.0543 mL | 0.2715 mL | 0.5430 mL | 1.3576 mL | |
| 60 mM | 0.0453 mL | 0.2263 mL | 0.4525 mL | 1.1313 mL | |
| 80 mM | 0.0339 mL | 0.1697 mL | 0.3394 mL | 0.8485 mL | |
| 100 mM | 0.0272 mL | 0.1358 mL | 0.2715 mL | 0.6788 mL |
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