MRK-016
Based on 2 publication(s) in Google Scholar
MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively; MRK-016 also readily penetrates the CNS.
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- Pureza: 99.71%
- No. CAS: 342652-67-9
- Fòrmula: C17H20N8O2
- Peso molecular:368.39
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
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Help & FAQs
Publications Citing Use of MedChemExpress (MCE) MRK-016
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Actividad biológica
Descripciòn
IC50 & Target
EC50: 3 nM (GABAA α5)[1]
Ki: 0.83 nM (Human GABAA α1β3γ2), 0.85 nM (Human GABAA α2β3γ2), 0.77 nM (Human GABAA α3β3γ2), 1.4 nM (Human GABAA α5β3γ2)[1]
In Vitro
MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor, with an EC50 of 3 nM for GABAA α5, and Kis of 0.83, 0.85, 0.77 and 1.4 nM for human GABAA α1β3γ2, GABAA α2β3γ2, GABAA α3β3γ2, and GABAA α5β3γ2, respectively[1][2]. MRK-016 is a full inverse agonist at the α5-subtype, shows very weak affinity at the GABAA α4β3γ2-subtype (Ki 395 nM) and is essentially inactive at the GABAA α6β3γ2 receptor (Ki > 4000 nM)[1]. MRK-016 shows a weak effect on GABAA α4β3γ2 with a Ki of 400 nM. MRK-016 (100 nM) alao increases long-term potentiation in mouse hippocampal slices[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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No. CAS 342652-67-9
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Appearance Solid
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Peso molecular 368.39
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Fòrmula C17H20N8O2
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Color White to off-white
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SMILES
CN1N=CN=C1COC2=NN3C(C4=NOC(C)=C4)=NN=CC3=C2C(C)(C)C
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (2)
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Journal Impact Factor
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Most Recent
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Nature
2025 Jul;643(8072):744-754. PMID: 40533550 -
Solvente y solubilidad
In Vitro:
DMSO : 50 mg/mL (135.73 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
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: ≥ 2.75 mg/mL (7.46 mM); Clear solution
This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 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.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.75 mg/mL (7.46 mM); Clear solution
This protocol yields a clear solution of ≥ 2.75 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (27.5 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
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.
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.
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.
Protocolo
Kinase Assay[1]
L(tk-) cells expressing human recombinant GABAA receptors containing β3- and γ2-subunits in combinatioon with various α-subunits are harvested and binding performed. The displacement of [3H]Ro 15-1788 binding by the test compounds (MRK-016, etc.) is measured in GABAA receptors containing eigher an α1-, α2-, α3-, and α5-subunit and from the IC50 and the Ki is calculated assuming respective Kd values of [3H]Ro 15-1788 binding of 0.92, 1.05, 0.58 and 0.45 nM at the α1-, α2-, α3-, and α5-subtypes. Nonspecific binding is defined by the inclusion of 10 μM flunitrazepam for the α1-, α2-, α3-, and α5-subtypes. The percentage inhibition of [3H]Ro 15-1788, the IC50 and the Ki values are calculated using ActivityBase[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration[1]
Mice[1]
The proconvulsant potential MRK-016 is determined in this assay. The convulsant is pentylenetetrazole which is dosed at 15 mg/mL with an infusion rate of 0.2 mL/min. This rate is chosen to ensure that drug-naive mince reach the terminal convulsion sign within 1 min. MRK-016 is dosed intraperitoneally (ip) at a concentration of 1, 3, and 10 mg/kg in 70% PEG 300[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureza y Documentación
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Ficha de datos (284 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Chambers MS, et al. An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties. J Med Chem. 2004 Nov 18;47(24):5829-32. [Content Brief]
[2]. Atack JR, et al. In vitro and in vivo properties of 3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)-pyrazolo[1,5-d]-[1,2,4]triazine (MRK-016), a GABAA receptor alpha5 subtype-selective inverse agonist. J Pharmacol Exp Ther. 2009 Nov;331(2):470-84. [Content Brief]
[3]. Eimerbrink MJ, et al. Administration of the inverse benzodiazepine agonist MRK-016 rescues acquisition and memory consolidation following peripheral administration of bacterial endotoxin. Behav Brain Res. 2015 Jul 15;288:50-3. [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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7145 mL | 13.5726 mL | 27.1451 mL | 67.8629 mL |
| 5 mM | 0.5429 mL | 2.7145 mL | 5.4290 mL | 13.5726 mL | |
| 10 mM | 0.2715 mL | 1.3573 mL | 2.7145 mL | 6.7863 mL | |
| 15 mM | 0.1810 mL | 0.9048 mL | 1.8097 mL | 4.5242 mL | |
| 20 mM | 0.1357 mL | 0.6786 mL | 1.3573 mL | 3.3931 mL | |
| 25 mM | 0.1086 mL | 0.5429 mL | 1.0858 mL | 2.7145 mL | |
| 30 mM | 0.0905 mL | 0.4524 mL | 0.9048 mL | 2.2621 mL | |
| 40 mM | 0.0679 mL | 0.3393 mL | 0.6786 mL | 1.6966 mL | |
| 50 mM | 0.0543 mL | 0.2715 mL | 0.5429 mL | 1.3573 mL | |
| 60 mM | 0.0452 mL | 0.2262 mL | 0.4524 mL | 1.1310 mL | |
| 80 mM | 0.0339 mL | 0.1697 mL | 0.3393 mL | 0.8483 mL | |
| 100 mM | 0.0271 mL | 0.1357 mL | 0.2715 mL | 0.6786 mL |
MRK-016 Related Classifications
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