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Purity: ≥98%
MRK-016 (MRK016; MRK 016) is a novel, potent, orally bioactive and selective negative allosteric modulator (inverse agonist) of α5 subunit-containing GABAA with nootropic properties. It has been found to produce rapid, ketamine-like antidepressant effects in animal models of depression. Also MRK-016 (MRK) can protect against memory acquisition and consolidation errors in mice. Post-training treatment with MRK-016 restored behavioral expression of fear in LPS-treated animals, despite elevated hippocampal Aβ, an effect that may be attributed to increased BDNF mRNA expression. Therefore, these data indicate that MRK-016 can prevent LPS- induced cognitive deficits associated with elevated Aβ, and restore hippocampal BDNF expression.
| 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 |
Behav Brain Res.2019 Feb 1;359:871-877.
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| Molecular Formula |
C17H20N8O2
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| Molecular Weight |
368.40
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| CAS # |
783331-24-8
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| Related CAS # |
783331-24-8;783331-24-8
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| SMILES |
CN1N=CN=C1COC2=NN3C(C4=NOC(C)=C4)=NN=CC3=C2C(C)(C)C
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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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 | 2.7144 mL | 13.5722 mL | 27.1444 mL | |
| 5 mM | 0.5429 mL | 2.7144 mL | 5.4289 mL | |
| 10 mM | 0.2714 mL | 1.3572 mL | 2.7144 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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