| Size | Price | Stock | Qty |
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| Targets |
MK-0343 targets the GABAA receptor, specifically acting as a subtype-selective partial agonist. It binds to GABAA receptors containing α1, α2, α3, and α5 subunits with high affinity. The compound has higher agonist efficacy at the α3 subtype compared to the α1 subtype. This selectivity for α3-containing receptors is thought to be responsible for its anxiolytic effects with reduced sedation, as sedation is primarily mediated by α1-containing receptors.
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| ln Vitro |
In vitro, MK-0343 binds to human recombinant GABAA receptors containing α1, α2, α3, and α5 subunits with high affinity. It acts as a partial agonist, meaning it produces a submaximal response even at full receptor occupancy. The compound shows higher agonist efficacy at the α3 subtype compared to α1. This differential efficacy is a key feature that distinguishes it from non-selective benzodiazepine full agonists. In electrophysiological assays, MK-0343 potentiates GABA-evoked currents in a subtype-dependent manner.
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| ln Vivo |
MK0343 readily penetrates the rat brain and occupies the benzodiazepine site of the GABAA receptor, with an Occ50 of 2.2 mg/kg po and a corresponding plasma EC50 of 115 ng as measured using an in vivo [3H]flumazenil binding assay. /mL[1] .
In vivo, MK-0343 was studied as a non-sedating anxiolytic in preclinical species (e.g., rodents). It demonstrated anxiolytic-like effects in animal models without causing sedation. However, in human clinical trials, the compound caused sedation, leading to its discontinuation. This species difference in sedative liability highlights the challenges in translating preclinical findings to humans for GABAA receptor modulators. |
| Enzyme Assay |
Non-cellular in vitro assays for MK-0343 involve receptor binding studies. A standard protocol uses membrane preparations from cells expressing recombinant human GABAA receptors containing various α subunits (α1, α2, α3, α5). The membranes are incubated with a radiolabeled ligand, such as [³H]flumazenil or [³H]Ro15-1788, and varying concentrations of MK-0343. Non-specific binding is determined in the presence of an excess of unlabeled flumazenil. After incubation, the reaction is terminated by rapid filtration, and the radioactivity bound is measured. The Ki values are calculated from the competition curves.
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| Cell Assay |
Cellular assays for MK-0343 are performed using cell lines expressing recombinant GABAA receptors, such as HEK293 or CHO cells transfected with different α subunit combinations. Cells are loaded with a calcium-sensitive dye or subjected to patch-clamp electrophysiology. GABA is applied to evoke currents, and the potentiation of these currents by MK-0343 is measured. The efficacy and potency at different receptor subtypes are compared. The compound's partial agonist activity is assessed by measuring the maximal potentiation relative to a full agonist.
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| Animal Protocol |
Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rat (approximately 250-300g) (pharmacokinetic/PK/PKs) [1]
Doses: 1, 2 or 3 mg/kg Route of Administration: Oral Experimental Results:Rapidly penetrates into the rat brain and occupies GABAA receptors For benzodiazepines in the body, the Occ50 is 2.2 mg/kg po, and the corresponding plasma EC50 is 115 ng/mL. In vivo animal studies for MK-0343 were conducted in rodent models of anxiety, such as the elevated plus maze or the light-dark box test. Animals were administered MK-0343 orally or intraperitoneally at doses such as 0.1-10 mg/kg. Anxiolytic-like effects were assessed by measuring the time spent in the open arms or the light compartment. Sedative effects were assessed using locomotor activity tests or the rotarod test. The compound showed anxiolytic effects without sedation in these models. |
| ADME/Pharmacokinetics |
MK-0343 has a molecular weight not specified in the available literature. It is a small molecule with drug-like properties. For in vivo studies, it can be formulated in vehicles such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. The compound is orally bioavailable, as it was tested in clinical trials. Detailed pharmacokinetic parameters, such as half-life, Cmax, and AUC, have not been fully reported.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for MK-0343 have not been extensively reported. In clinical trials, the compound caused sedation in humans, which was an adverse effect that led to its discontinuation. This indicates that the compound has central nervous system effects at therapeutic doses. As a research chemical, it is not intended for human use and is strictly for preclinical research purposes. Standard safety precautions should be followed.
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| References | |
| Additional Infomation |
MRK-409 is a GABA-A receptor agonist.
MK-0343 (MRK-409) is a GABAA receptor subtype-selective partial agonist that was investigated as a non-sedating anxiolytic. It binds with high affinity to GABAA receptors containing α1, α2, α3, and α5 subunits, with higher agonist efficacy at α3 than at α1. Despite showing non-sedating anxiolytic effects in preclinical species, it caused sedation in humans, leading to its discontinuation from clinical development. The compound remains a valuable research tool for studying the pharmacology of GABAA receptor subtypes. |
| Molecular Formula |
C19H17F2N7O
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|---|---|
| Molecular Weight |
397.3898
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| Exact Mass |
397.146
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| CAS # |
233275-76-8
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| PubChem CID |
22609888
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| Appearance |
White to off-white solid powder
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| LogP |
3.044
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
GOIFCXRIFSYPFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17F2N7O/c1-27-16(22-10-23-27)9-29-19-12(11-4-2-5-11)8-15-24-25-18(28(15)26-19)17-13(20)6-3-7-14(17)21/h3,6-8,10-11H,2,4-5,9H2,1H3
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| Chemical Name |
7-cyclobutyl-3-(2,6-difluorophenyl)-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine
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| Synonyms |
MK 0343 MK0343MK-0343 MRK409 MRK-409MRK 409
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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 : ~250 mg/mL (~629.12 mM)
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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 | 2.5164 mL | 12.5821 mL | 25.1642 mL | |
| 5 mM | 0.5033 mL | 2.5164 mL | 5.0328 mL | |
| 10 mM | 0.2516 mL | 1.2582 mL | 2.5164 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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