Size | Price | Stock | Qty |
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1mg |
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5mg |
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10mg |
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50mg |
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Other Sizes |
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Targets |
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]
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ln Vitro |
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 α1β3η2, GABAA α2β3η2, GABAA α3β3η2, and GABAA α5β3γ2, respectively, MRK-016 is a selective, orally bioavailable inverse agonist of GABAA α5 receptor. As a complete inverse agonist at the α5-subtype, MRK-016 exhibits very low affinity for the GABAA α4β3γ2-subtype (Ki 395 ± 173 nM), and at the GABAA α6β3γ2 receptor (Ki > 4000 nM), it is basically inactive[1]. At 400 nM, MRK-016 had a negligible impact on GABAA α4β3γ2. In mouse hippocampus slices, MRK-016 (100 nM) alao enhances long-term potentiation[2].
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ln Vivo |
For 20 days in mice, MRK-016 did not generate seizures at 30 mg/kg by po or worsen convulsions induced by pentylenetetrazole at 10 mg/kg via ip. In rats, MRK-016 does not exhibit overt anxiogenic-like effects at dosages that occupy more than 95% of the binding sites for benzodiazepines (BZs). In rats, MRK-016 (0.3, 1, and 3 mg/kg, po) dose-dependently enhances hippocampal-dependent memory task performance[1]. In rats, MRK-016 (0.3–30 mg/kg, po) results in excellent receptor occupancy. The delayed matching-to-position version of the Morris water maze exhibits cognitive-enhancing activity when administered at doses of 0.3, 1, or 3 mg/kg po. Mice treated with MRK -016 (1, 3, or 10 mg/kg ip) do not produce kindling[2]. In mice, MRK-016 (3 mg/kg, ip) prevents learning and memory deficits brought on by LPS[3].
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References |
[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.
[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. [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 |
Molecular Formula |
C17H20N8O2
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Molecular Weight |
368.39
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CAS # |
342652-67-9
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Appearance |
Solid powder
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SMILES |
CN1N=CN=C1COC2=NN3C(C4=NOC(C)=C4)=NN=CC3=C2C(C)(C)C
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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: 50 mg/mL (135.73 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (7.46 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 27.5 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: ≥ 2.75 mg/mL (7.46 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.75 mg/mL (7.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.7145 mL | 13.5726 mL | 27.1451 mL | |
5 mM | 0.5429 mL | 2.7145 mL | 5.4290 mL | |
10 mM | 0.2715 mL | 1.3573 mL | 2.7145 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.