| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
α1 GABA(A) receptor 1.2 nM (Ki) α2 GABA(A) receptor 1.0 nM (Ki) α3 GABA(A) receptor 0.73 nM (Ki) α5 GABA(A) receptor 0.50 nM (Ki)
MRK-898 targets the benzodiazepine binding site on GABAA receptors, functioning as a positive allosteric modulator (PAM). It binds to the alpha1, alpha2, alpha3, and alpha5 subunits with high affinity: Ki values of 1.2 nM (alpha1), 1.0 nM (alpha2), 0.73 nM (alpha3), and 0.50 nM (alpha5). This broad-spectrum binding profile defines its pharmacology. |
|---|---|
| ln Vitro |
In vitro, MRK-898 is a potent high-affinity ligand for multiple GABAA receptor subunits. It binds to alpha1, alpha2, alpha3, and alpha5 subunits in the low nanomolar range (Ki of 1.2, 1.0, 0.73, and 0.50 nM, respectively). This suggests it is a highly effective modulator that potentiates the effects of GABA at the GABAA receptor complex.
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| ln Vivo |
In vivo, MRK-898 has been described as an orally active GABAA receptor modulator. Preclinical studies suggest its potential therapeutic applications in neurological disorders such as anxiety and sleep disorders, given that alpha2/alpha3 subunit-containing receptors are associated with anxiolytic effects, while alpha1-containing receptors are linked to sedation.
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| Enzyme Assay |
Non-cellular assays for MRK-898 are standard radioligand binding assays. Membranes from cells expressing specific human recombinant GABAA receptor subunits (alpha1beta3gamma2, alpha2beta3gamma2, alpha3beta3gamma2, or alpha5beta3gamma2) are incubated with [3H]flumazenil (a benzodiazepine site antagonist) and varying concentrations of MRK-898. Bound radioactivity is measured after filtration to calculate Ki values.
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| Cell Assay |
Cellular protocols for GABAA PAMs typically use electrophysiology. HEK-293 cells are transfected with cDNAs encoding GABAA receptor subunits. Using the whole-cell patch-clamp technique, cells are voltage-clamped at -60 mV and GABA is applied. The potentiation of GABA-evoked current (Ipeak) by co-application of MRK-898 is measured to determine its efficacy as a PAM.
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| Animal Protocol |
No specific in vivo animal protocol for MRK-898 is provided. A standard protocol for testing anxiolytic activity is the elevated plus maze in rats. MRK-898 would be administered orally, and 30-60 minutes later, the time spent in the open arms of the maze is recorded, as increased open arm time indicates anxiolysis. Sedative effects can be assessed by locomotor activity.
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| ADME/Pharmacokinetics |
No specific PK data is provided, but MRK-898 is described as an “orally bioavailable” modulator. This indicates it is absorbed from the GI tract and can reach the central nervous system to exert its effects. Further studies would be needed to determine its half-life, Cmax, and brain penetration.
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| Toxicity/Toxicokinetics |
No specific toxicological data is provided. The safety profile of non-selective GABAA PAMs is well-established; they can cause sedation, tolerance, and physical dependence. As a broad-spectrum PAM, MRK-898 would likely induce these effects. Research aims to identify subunit-selective modulators to separate anxiolytic activity from sedative liability.
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| References | |
| Additional Infomation |
MRK-898 is a research compound that binds to the benzodiazepine site on GABAA receptors. Its Ki values highlight the classic structure-activity relationship (SAR) of non-selective GABAA modulators. It is valuable for investigating the therapeutic potential of targeting specific receptor combinations (alpha2/alpha3 for anxiety, alpha5 for cognition) versus the more sedating alpha1 pathway.
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| Molecular Formula |
C20H9F5N4
|
|---|---|
| Molecular Weight |
400.304280996323
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| Exact Mass |
400.074
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| CAS # |
461450-30-6
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| PubChem CID |
9843909
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
29
|
| Complexity |
634
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1=CC(=C(C=C1C2=CN=C3N2C=CC(=N3)C(F)(F)F)C4=C(C=C(C=C4)F)C#N)F
|
| InChi Key |
XXRKXVKJMSIZSM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H9F5N4/c21-13-2-3-14(12(7-13)9-26)15-8-11(1-4-16(15)22)17-10-27-19-28-18(20(23,24)25)5-6-29(17)19/h1-8,10H
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| Chemical Name |
5-fluoro-2-[2-fluoro-5-[7-(trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl]phenyl]benzonitrile
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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: ~100 mg/mL (~249.8 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.25 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4981 mL | 12.4906 mL | 24.9813 mL | |
| 5 mM | 0.4996 mL | 2.4981 mL | 4.9963 mL | |
| 10 mM | 0.2498 mL | 1.2491 mL | 2.4981 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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