| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
cannabinoid type-2 receptors
CB2R PAM targets the cannabinoid type 2 receptor (CB2R) as a positive allosteric modulator. Unlike orthosteric agonists, allosteric modulators bind to a site distinct from the agonist binding site and enhance the receptor's response to endogenous or exogenous agonists. CB2R PAM enhances CP55940- and 2-arachidonoylglycerol-stimulated [35S]GTPγS binding to CB2 receptors. This allosteric modulation allows for enhanced CB2 signaling without directly activating the receptor, potentially providing more selective and safer therapeutic effects. |
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| ln Vitro |
The capacity of CP55940 and 2-AG, but not AEA, to activate [35S]GTPγS binding to CB2Rs is greatly increased by CB2R PAM (100 nM)[1].
In vitro, CB2R PAM enhances CP55940- and 2-arachidonoylglycerol-stimulated [35S]GTPγS binding to CB2 receptors, but has no effect in the absence of an agonist. This demonstrates its positive allosteric modulator activity, where the compound potentiates the effects of agonists without having intrinsic activity of its own. Standard in vitro assays include [35S]GTPγS binding assays in membrane preparations from cells expressing CB2 receptors, as well as functional assays measuring downstream signaling pathways (e.g., cAMP accumulation, ERK phosphorylation) in the presence and absence of agonists. |
| ln Vivo |
CB2R PAM exhibits antinociceptive action at doses of 1–20 mg/kg; po[1].
In vivo, CB2R PAM displays antinociceptive activity in an experimental mouse model of neuropathic pain. The compound is orally active, which is advantageous for therapeutic development. Its positive allosteric modulation of CB2R enhances endogenous cannabinoid signaling at CB2 receptors, producing analgesic effects without the psychoactive side effects associated with CB1 receptor activation. The compound is used in research to explore therapeutic strategies for inflammation, pain, neuroprotection, and immune-related disorders. |
| Enzyme Assay |
For non-cell-based receptor binding assays, CB2R PAM can be evaluated using membrane preparations from cells expressing human CB2 receptors. [35S]GTPγS binding assays are performed in the presence of a CB2 agonist (CP55940 or 2-arachidonoylglycerol) and increasing concentrations of the test compound. Membrane preparations are incubated with GDP, [35S]GTPγS, the agonist, and the test compound. The amount of bound [35S]GTPγS is measured by filtration. Enhancement of agonist-stimulated [35S]GTPγS binding compared to agonist alone indicates positive allosteric modulator activity.
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| Cell Assay |
For in vitro cellular assays, cells expressing human CB2 receptors are cultured in appropriate media. For functional assays, cells are treated with a CB2 agonist (CP55940 or 2-arachidonoylglycerol) in the presence or absence of CB2R PAM. Downstream signaling markers such as cAMP levels (measured by ELISA or HTRF), ERK phosphorylation (measured by Western blot), or β-arrestin recruitment (measured by BRET or enzyme complementation) are assessed. The potentiation of agonist-induced signaling by the compound confirms its positive allosteric modulator activity.
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| Animal Protocol |
Animal/Disease Models: Male CD-1 albino mice (Oxaliplatin-induced neuropathic pain model)[1]
Doses: 1, 5, 10, 20 mg/ kg Route of Administration: Po Experimental Results: Dramatically increased licking latency in the animals starting from 5 mg/kg. For in vivo animal studies, CB2R PAM is administered orally to rodents. In neuropathic pain models (e.g., spinal nerve ligation, chronic constriction injury, or chemotherapy-induced neuropathy), mechanical allodynia and thermal hyperalgesia are assessed using von Frey filaments and hot plate tests. In inflammation models, inflammatory markers and paw swelling are assessed. In neuroprotection models, neurological scores and tissue damage are evaluated. Dosing regimens vary depending on the specific model. Blood and tissue samples may be collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
CB2R PAM is an orally active compound. Based on its molecular weight of 435.33 and molecular formula of C21H24BrFN2O2, the compound is expected to have good oral bioavailability. The compound appears as a white to off-white solid powder. Comprehensive pharmacokinetic studies would include assessment of oral bioavailability, half-life, protein binding, and tissue distribution. The compound should be stored at -20°C for long-term stability.
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| Toxicity/Toxicokinetics |
The toxicity profile of CB2R PAM has not been extensively reported. As a positive allosteric modulator of CB2R, it is expected to have a favorable safety profile, as it only enhances signaling in the presence of endogenous agonists and does not directly activate the receptor. The compound is for research use only and not for human consumption. Standard toxicological evaluation would include acute and repeated-dose toxicity studies, as well as assessment of effects on the immune system and other organ systems.
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| References | |
| Additional Infomation |
CB2R PAM is an orally active positive allosteric modulator of the cannabinoid type 2 receptor (CB2R). It enhances agonist-stimulated CB2 receptor signaling without having intrinsic activity. The compound displays antinociceptive activity in neuropathic pain models and is used in research to explore therapeutic strategies for inflammation, pain, neuroprotection, and immune-related disorders. Its allosteric mechanism offers potential advantages over direct agonists, including improved selectivity and reduced side effects. The compound is available for research purposes only.
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| Molecular Formula |
C21H24BRFN2O2
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| Molecular Weight |
435.33
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| Exact Mass |
434.1
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| CAS # |
2244579-87-9
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| PubChem CID |
137553165
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
572.4±50.0 °C at 760 mmHg
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| Flash Point |
300.0±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.605
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| LogP |
4.78
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
630
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C(=O)N(C=C1Br)CC2=CC=C(C=C2)F)NC(=O)C3CCCCCC3
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| InChi Key |
NSGDYZCDUPSTQT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H24BrFN2O2/c1-14-18(22)13-25(12-15-8-10-17(23)11-9-15)21(27)19(14)24-20(26)16-6-4-2-3-5-7-16/h8-11,13,16H,2-7,12H2,1H3,(H,24,26)
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| Chemical Name |
N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide
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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 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)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (114.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.74 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2971 mL | 11.4855 mL | 22.9711 mL | |
| 5 mM | 0.4594 mL | 2.2971 mL | 4.5942 mL | |
| 10 mM | 0.2297 mL | 1.1486 mL | 2.2971 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/NCT01435837
Conditions:Voice DisordersProducts are for research use only; We do not sell to patients
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