| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg | |||
| Other Sizes |
| Targets |
Fatty Acid Amide Hydrolase (FAAH). SSR411298 is a selective and reversible FAAH inhibitor. By blocking FAAH, it prevents the degradation of several bioactive lipid amides, including anandamide (AEA), oleoylethanolamide (OEA), and palmitoylethanolamide (PEA), thereby potentiating endocannabinoid signaling.
|
|---|---|
| ln Vitro |
Mouse brain FAAH is inhibited by SSR411298 (0.1, 1, 10, 100, 1000, and 10,000 nM) in a concentration-dependent manner[1]. The ex-vivo trial with SSR411298 results in maximum inhibition of FAAH between 0.3 and 30 mg/kg[1].
In vitro, SSR411298 is a potent and selective inhibitor of mouse brain FAAH, with an IC50 of 62.5 nM. This potency and selectivity for FAAH make it effective at increasing levels of its substrates without directly activating cannabinoid receptors, distinguishing it from direct-acting CB1 agonists. |
| ln Vivo |
In the rat forced-swimming test and the mouse chronic mild stress model, SSR411298 (0.3, 1, 3 mg/kg; po; twice a day during 2 days; 60 minutes before pretest, immediately after, and 60 minutes before the second session of testing) produces robust antidepressant-like activity, notably restoring the development of inadequate coping responses to chronic stress in male Wistar rats weighing 235-290 g[1]. In the hippocampus, SSR411298 (0.3, 1, 3, 10 mg/kg; po; single dose; two hours before sacrifice) significantly raises tissular AEA, PEA, and OEA levels globally, but not 2-AG levels[1].
In vivo, SSR411298 potently increases hippocampal levels of AEA, OEA, and PEA in mice, confirming its ex vivo target engagement. It restores the development of maladaptive behaviors to acute and chronic stress in rodents. Despite elevating endocannabinoid levels, it did not produce the memory deficits or motor impairment (side effects) evoked by direct-acting cannabinoids. |
| Enzyme Assay |
The standard non-cellular assay for FAAH inhibition is a radiometric assay using [3H]anandamide as a substrate. Mouse brain FAAH is incubated with varying concentrations of SSR411298 in a reaction buffer (e.g., 125 mM Tris-HCl, pH 9.0, 1 mM EDTA, 0.1% BSA). After a pre-incubation, [3H]anandamide is added. The reaction is stopped by adding activated charcoal, and the released [3H]ethanolamine is measured by scintillation counting.
|
| Cell Assay |
Cell-based assays for FAAH inhibitors typically involve incubation with a cell line known to express FAAH (e.g., mouse Neuro2a cells). Cells are treated with SSR411298, then harvested and lysed. The FAAH activity in the lysate is then measured using a fluorogenic substrate (e.g., arachidonoyl 7-amino-4-methylcoumarin amide) to determine the inhibition of the enzyme in a cellular environment.
|
| Animal Protocol |
In an in vivo stress-restoration study, mice are subjected to an acute or chronic stress paradigm. SSR411298 (0.3, 1, 3 mg/kg, p.o.) is administered twice a day for 2 days, 60 minutes before the pretest. Behavioral endpoints such as immobility in forced swim test (depression-like) or marble burying (anxiety-like) are recorded. Ex vivo brain FAAH activity is also measured.
|
| ADME/Pharmacokinetics |
No detailed PK data is provided, but SSR411298 is described as orally active. In human clinical trials, plasma samples were collected to evaluate PK exposure. In mice, maximal ex vivo FAAH inhibition is observed between 0.3 and 30 mg/kg, indicating a dose-response relationship that correlates with the drug's absorption and distribution.
|
| Toxicity/Toxicokinetics |
No detailed toxicological data is provided, but the compound was advanced to Phase II clinical trials for major depressive disorder and cancer pain. In animal models, it was well-tolerated. Importantly, it did not produce the memory deficits or motor impairment typically seen with direct CB1 agonists, suggesting a favorable safety profile.
|
| References | |
| Additional Infomation |
SSR411298 reached Phase II clinical development for the treatment of major depressive disorder (MDD) in elderly patients and as an adjunctive treatment for persistent cancer pain. It represents a first-in-class approach to treating CNS disorders by indirect modulation of endocannabinoid tone, offering a potential alternative to direct-acting cannabinoids with fewer psychoactive side effects.
|
| Molecular Formula |
C21H26N2O6
|
|---|---|
| Molecular Weight |
402.440946102142
|
| Exact Mass |
402.179
|
| CAS # |
666860-59-9
|
| PubChem CID |
44482551
|
| Appearance |
White to light yellow solid powder
|
| LogP |
2.2
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
29
|
| Complexity |
537
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C(CCCNC(=O)OCC(N)=O)OCC(C2=CC=CC3C=C(C=CC2=3)OC)C1
|
| InChi Key |
OGKKHZMANPWMSD-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H26N2O6/c1-26-16-7-8-18-14(10-16)4-2-5-17(18)15-11-27-20(28-12-15)6-3-9-23-21(25)29-13-19(22)24/h2,4-5,7-8,10,15,20H,3,6,9,11-13H2,1H3,(H2,22,24)(H,23,25)
|
| Chemical Name |
(2-amino-2-oxoethyl) N-[3-[5-(6-methoxynaphthalen-1-yl)-1,3-dioxan-2-yl]propyl]carbamate
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (248.48 mM)
|
|---|---|
| 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 | 2.4848 mL | 12.4242 mL | 24.8484 mL | |
| 5 mM | 0.4970 mL | 2.4848 mL | 4.9697 mL | |
| 10 mM | 0.2485 mL | 1.2424 mL | 2.4848 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
