| Size | Price | Stock | Qty |
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| 5mg |
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| 1g | |||
| Other Sizes |
| Targets |
MK-4409 specifically targets fatty acid amide hydrolase (FAAH), a serine hydrolase enzyme that is responsible for the intracellular hydrolysis of a diverse family of fatty acid amides, including the endocannabinoid anandamide and the anti-inflammatory lipid oleamide. By binding to the enzyme's active site, MK-4409 acts as a potent and reversible inhibitor, blocking its catalytic activity. This inhibition leads to a significant increase in the levels of anandamide in the central nervous system and periphery. Elevated anandamide then acts as an endogenous agonist at the cannabinoid CB1 and CB2 receptors, modulating pain signaling and reducing inflammation. The compound's ability to cross the blood-brain barrier is crucial for its effects on central pain pathways. Its mechanism is characterized by high selectivity for FAAH, minimizing off-target effects on other serine hydrolases and enzymes.
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| ln Vitro |
In vitro studies have characterized MK-4409 as a potent and selective FAAH inhibitor. Enzyme activity assays have demonstrated its ability to inhibit FAAH with an IC50 of 11 nM. These assays typically involve incubating the FAAH enzyme with a radiolabeled or fluorogenic substrate in the presence of varying concentrations of MK-4409. The inhibition of substrate hydrolysis is then measured to calculate the IC50. Selectivity profiling against other serine hydrolases has confirmed its specificity for FAAH. These in vitro data are fundamental for confirming its mechanism of action as a selective and potent FAAH inhibitor.
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| ln Vivo |
In vivo, MK-4409 has been investigated for its efficacy in models of inflammatory and neuropathic pain. Its brain-penetrant properties are essential for its central activity. In animal models, such as the formalin test, the carrageenan-induced paw edema model, or the chronic constriction injury (CCI) model of neuropathic pain, administration of MK-4409 has been shown to produce significant analgesic and anti-inflammatory effects. These effects are attributed to the elevation of anandamide levels in the brain and spinal cord, which then activate CB1 and CB2 receptors to modulate pain pathways. The compound's efficacy in these models supports its potential as a therapeutic for chronic pain conditions.
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| Enzyme Assay |
The in vitro enzyme/receptor binding assay for MK-4409 involves measuring the inhibition of FAAH activity. In these assays, the FAAH enzyme, typically recombinant human FAAH, is incubated with its substrate, anandamide, in the presence of varying concentrations of MK-4409. The hydrolysis of anandamide to arachidonic acid and ethanolamine is then measured. This can be done using radiolabeled anandamide, where the released arachidonic acid is quantified by scintillation counting, or using a fluorescent substrate, where the increase in fluorescence is measured. The IC50 is determined from the dose-response curves. These assays are the primary method for quantifying the compound's potency as a FAAH inhibitor.
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| Cell Assay |
Cellular assays for MK-4409 are conducted to confirm its functional activity in a biological context. These assays typically involve treating cells that express FAAH, such as neuroblastoma cells or primary neurons, with MK-4409. The levels of anandamide and other fatty acid amides are then measured by LC-MS/MS. An increase in anandamide levels confirms that the compound is inhibiting FAAH activity within the cell. The functional consequence of this elevation, such as the activation of downstream signaling pathways (e.g., ERK phosphorylation) or the modulation of neuronal activity, can also be assessed. These cell-based assays are essential for confirming that the biochemical inhibition translates to functional effects in a cellular environment.
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| Animal Protocol |
In vivo animal experiments for MK-4409 are conducted in various pain models. In the formalin test, the compound is typically administered orally or intraperitoneally, and the reduction of pain-related behaviors (licking and flinching of the injected paw) is measured. In neuropathic pain models, such as the spinal nerve ligation or CCI model, the increase in paw withdrawal thresholds to mechanical or thermal stimuli is measured after drug administration. The compound's effects on inflammatory pain can be assessed using the carrageenan-induced paw edema model, where both the reduction of paw swelling and pain behaviors are measured. These in vivo studies are crucial for evaluating its therapeutic potential and for understanding its pharmacokinetic and pharmacodynamic properties.
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| ADME/Pharmacokinetics |
MK-4409 has a molecular weight of 441.91 g/mol and a molecular formula of C22H17ClFN3O2S. It is a solid and is typically soluble in DMSO. For storage, it should be kept at -20°C. It is known to be brain-penetrant, a key property for its central nervous system activity.
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| Toxicity/Toxicokinetics |
The toxicity profile of MK-4409 is limited. As a research-grade compound, comprehensive toxicological evaluations are not widely published. However, as with other FAAH inhibitors, potential side effects may be related to the modulation of the endocannabinoid system and could include effects on mood, appetite, and gastrointestinal function. Its selectivity for FAAH is a key feature for minimizing off-target toxicity.
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| References | |
| Additional Infomation |
MK-4409 is a potent, selective, and brain-penetrant inhibitor of fatty acid amide hydrolase (FAAH) developed for the research of inflammatory and neuropathic pain. Its mechanism of action involves the inhibition of FAAH, leading to increased levels of anandamide and subsequent activation of the endocannabinoid system. As a research compound, MK-4409 has not received regulatory approval and is a valuable tool for studying the role of FAAH in pain and inflammation, contributing to the understanding of the endocannabinoid system as a therapeutic target.
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| Molecular Formula |
C22H17CLFN3O2S
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|---|---|
| Molecular Weight |
441.91
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| Exact Mass |
441.071
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| CAS # |
1207745-58-1
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| PubChem CID |
53341130
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.969
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
567
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CN=C(C=C1)SC1=C(C2=CN=C(C=C2)C(C)(C)O)N=C(C2C=CC(=CC=2)F)O1
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| InChi Key |
DBZMCSVIITXLCC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H17ClFN3O2S/c1-22(2,28)17-9-5-14(11-25-17)19-21(30-18-10-6-15(23)12-26-18)29-20(27-19)13-3-7-16(24)8-4-13/h3-12,28H,1-2H3
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| Chemical Name |
2-[5-[5-(5-chloropyridin-2-yl)sulfanyl-2-(4-fluorophenyl)-1,3-oxazol-4-yl]pyridin-2-yl]propan-2-ol
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| Synonyms |
MK4409; MK 4409; MK-4409
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.2629 mL | 11.3145 mL | 22.6290 mL | |
| 5 mM | 0.4526 mL | 2.2629 mL | 4.5258 mL | |
| 10 mM | 0.2263 mL | 1.1315 mL | 2.2629 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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