| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Cannabinoid receptor type 2 (CB2R). S-777469 is a selective and orally active agonist of CB2R, with a Ki of 36 nM. It shows high selectivity for CB2R over other cannabinoid receptor subtypes. The activation of CB2R is responsible for its antipruritic effects, which are reversed by the CB2-selective antagonist SR144528.
|
|---|---|
| ln Vitro |
In vitro, S-777469 acts as a selective CB2R agonist with a Ki of 36 nM, demonstrating high affinity for the receptor. Its mechanism of action involves activation of peripheral CB2 receptors, which leads to the inhibition of itch signal transmission without directly blocking histamine or other pruritogens.
|
| ln Vivo |
In vivo, S-777469 significantly suppresses scratching behavior in rodents induced by various pruritogenic agents, including compound 48/80, histamine, substance P (in mice), and serotonin (in rats) in a dose-dependent manner. The antipruritic effects are completely reversed by pre-treatment with the CB2-selective antagonist SR144528, confirming target-mediated activity. Additionally, S-777469 inhibits histamine-induced peripheral nerve firing in mice.
|
| Enzyme Assay |
The binding affinity of S-777469 for CB2R is determined via a standard radioligand competition binding assay. Membranes from CHO cells stably expressing human CB2R are incubated with [3H]WIN55,212-2 and varying concentrations of S-777469 in assay buffer. After incubation, bound and free radioligands are separated by rapid filtration through glass fiber filters, and retained radioactivity is measured by liquid scintillation counting to calculate the Ki.
|
| Cell Assay |
Functional CB2R activation is assessed by measuring the inhibition of forskolin-stimulated cAMP accumulation. CHO cells expressing human CB2R are pre-treated with varying concentrations of S-777469 in the presence of forskolin and the phosphodiesterase inhibitor IBMX. After incubation, cAMP levels are quantified using a homogeneous time-resolved fluorescence (HTRF) assay kit, and EC50 values for receptor activation are calculated.
|
| Animal Protocol |
In an in vivo scratching behavior model, male ICR mice are fasted and then orally administered S-777469 (e.g., 0.3, 1, 3, 10 mg/kg) 60 minutes before an intradermal injection of compound 48/80 (a pruritogenic agent) into the rostral back. Mice are then placed in an observation chamber, and the total number of scratching bouts is counted over a 30-60 minute period. A reduction in scratching behavior indicates antipruritic efficacy.
|
| ADME/Pharmacokinetics |
Specific pharmacokinetic data for S-777469 is not fully detailed, but it is characterized as an "orally active" compound, indicating it is absorbed and systemically bioavailable. The effective dose range in mouse models (1-10 mg/kg p.o.) suggests appropriate exposure levels for target engagement. As a selective CB2R agonist, it is not expected to cross the blood-brain barrier extensively.
|
| Toxicity/Toxicokinetics |
S-777469 progressed to Phase II clinical trials for the treatment of atopic dermatitis. In preclinical studies, it was well-tolerated at effective doses. The selectivity for CB2R over CB1R is crucial for its safety profile, as it avoids CNS-mediated side effects such as psychoactivity, memory impairment, and dependence that are associated with CB1R activation.
|
| References |
|
| Additional Infomation |
S-777469 is being studied in the clinical trial NCT00703573 (a randomized, double-blind study designed to evaluate the safety and efficacy of two doses of S-777469 in patients with atopic dermatitis).
S-777469 was originally developed by Shionogi & Co., Ltd., and successfully completed Phase II clinical trials for atopic dermatitis. Unlike traditional antihistamines which only target histamine-induced itch, S-777469 inhibits itch signals induced by multiple pruritogens (including substance P and serotonin) via CB2 receptor agonism, making it a novel and broader-acting antipruritic mechanism. |
| Molecular Formula |
C23H27FN2O4
|
|---|---|
| Molecular Weight |
414.47
|
| Exact Mass |
414.195
|
| CAS # |
885496-53-7
|
| PubChem CID |
57331749
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.4
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
30
|
| Complexity |
759
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1(NC(C2=CC(C)=C(CC)N(CC3=CC=C(F)C=C3)C2=O)=O)(C(O)=O)CCCCC1
|
| InChi Key |
JIYXOJFSPOFZPY-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C23H27FN2O4/c1-3-19-15(2)13-18(20(27)25-23(22(29)30)11-5-4-6-12-23)21(28)26(19)14-16-7-9-17(24)10-8-16/h7-10,13H,3-6,11-12,14H2,1-2H3,(H,25,27)(H,29,30)
|
| Chemical Name |
1-[[6-ethyl-1-[(4-fluorophenyl)methyl]-5-methyl-2-oxopyridine-3-carbonyl]amino]cyclohexane-1-carboxylic acid
|
| 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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 83.33 mg/mL (201.05 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 | 2.4127 mL | 12.0636 mL | 24.1272 mL | |
| 5 mM | 0.4825 mL | 2.4127 mL | 4.8254 mL | |
| 10 mM | 0.2413 mL | 1.2064 mL | 2.4127 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.
Link: https://clinicaltrials.gov/ct2/show/NCT00703573
Conditions:Atopic DermatitisLink: https://clinicaltrials.gov/ct2/show/NCT00697710
Conditions:Atopic DermatitisProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
