| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
CB2[1]
Cannabinoid receptor type 2 (CB2R). Vicasinabin is a potent and selective full agonist of CB2R, with no detectable binding or activation of the central cannabinoid receptor type 1 (CB1R). It has an EC50 of 2.8 nM for receptor activation and a Ki of 51.3 nM for binding affinity. |
|---|---|
| ln Vitro |
In vitro, Vicasinabin is a potent and highly selective CB2R agonist. It demonstrates full agonism in both recombinant (human and mouse CB2R expressed in CHO cells) and endogenous (human Jurkat cells, rat/mouse spleen cells) expression systems. Its functional potency translates well across different cellular backgrounds. It exhibits no CB1R binding or activation.
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| ln Vivo |
In vivo, orally administered Vicasinabin reduces retinal vascular permeability, leukocyte adhesion (leukostasis), and choroidal neovascularization (CNV) in rodent models of retinal disease. It shows efficacy in LPS-induced uveitis, STZ-induced diabetic retinopathy (DR), and laser-induced CNV with an ED50 of 0.32 mg/kg, demonstrating potent anti-inflammatory and anti-permeability effects.
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| Enzyme Assay |
The binding affinity of Vicasinabin is determined using a standard radioligand competition binding assay. Membranes from CHO cells expressing human recombinant CB2R are incubated with [3H]CP-55,940 (a non-selective cannabinoid agonist) and varying concentrations of the test compound in assay buffer for 60-90 min at 30degC. Nonspecific binding is defined with 10 uM unlabeled CP-55,940, and bound radioactivity is separated by filtration.
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| Cell Assay |
Functional activity is assessed using a cAMP accumulation assay. CHO cells expressing human CB2R are pre-incubated with forskolin to elevate cAMP levels, then treated with varying concentrations of Vicasinabin. CB2R activation inhibits adenylyl cyclase, reducing cAMP levels. After 30 min of incubation, cAMP concentrations are quantified using a homogeneous time-resolved fluorescence (HTRF) kit or a competitive ELISA.
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| Animal Protocol |
A standard in vivo protocol for assessing retinal efficacy uses the streptozotocin (STZ)-induced diabetic retinopathy model in rats. STZ (55 mg/kg) is injected intraperitoneally to induce diabetes. Two weeks later, animals receive daily oral doses of Vicasinabin (0.3, 1, 3, or 10 mg/kg) for 4 weeks. Retinal vascular permeability is measured using the Evans blue extravasation technique, and leukocyte adhesion is quantified by counting adherent leukocytes in retinal vessels.
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| ADME/Pharmacokinetics |
Vicasinabin exhibits a favorable ADMET (Absorption, Distribution, Metabolism, Elimination, Toxicity) profile and demonstrates systemic and ocular exposure after oral delivery. It is highly selective with no CB1R activity, significantly reducing the risk of CNS side effects. The compound is orally bioavailable, supporting once-daily dosing in preclinical models.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided beyond the ADMET profile, which is described as favorable. The absence of detectable CB1R binding or activation suggests a significantly lower risk of the classic CNS-mediated adverse effects associated with CB1R agonists, such as psychotropic effects, memory impairment, and motor incoordination, supporting a good preclinical safety margin.
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| References | |
| Additional Infomation |
Vicasinabin is a small molecule drug. Currently, the clinical trial NCT04265261 (a study investigating the efficacy and safety of RG7774 in treating untreated type 1 or type 2 diabetes patients with diabetic retinopathy) is underway. The monoisotope molecular weight of vicassinabin is 358.2 Da.
Vicasinabin (RG7774) was developed through lead optimization of a high-throughput screening hit by Hoffmann-La Roche. It represents a novel class of CB2R agonists with high selectivity and oral bioavailability. Its preclinical efficacy in multiple rodent models of retinal pathology has advanced it as a potential therapeutic candidate for treating diabetic retinopathy and other chronic inflammatory retinal diseases. |
| Molecular Formula |
C15H22N10O
|
|---|---|
| Molecular Weight |
358.40158033371
|
| Exact Mass |
358.197
|
| CAS # |
1433361-02-4
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| PubChem CID |
86296048
|
| Appearance |
White to off-white solid powder
|
| LogP |
0.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
501
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O[C@H]1CCN(C2C3=C(N(CC4=NN=NN4C)N=N3)N=C(C(C)(C)C)N=2)C1
|
| InChi Key |
MAYZWDRUFKUGGP-VIFPVBQESA-N
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| InChi Code |
InChI=1S/C15H22N10O/c1-15(2,3)14-16-12(24-6-5-9(26)7-24)11-13(17-14)25(21-19-11)8-10-18-20-22-23(10)4/h9,26H,5-8H2,1-4H3/t9-/m0/s1
|
| Chemical Name |
(3S)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol
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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: 125 mg/mL (348.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7902 mL | 13.9509 mL | 27.9018 mL | |
| 5 mM | 0.5580 mL | 2.7902 mL | 5.5804 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7902 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/NCT04265261
Conditions:Diabetic RetinopathyProducts are for research use only; We do not sell to patients
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