Org 27569
Based on 1 Customer Validation
Org 27569 is a potent CB1 receptor allosteric modulator, which increases agonist binding, yet blocks agonist-induced CB1 signaling.
For research use only. We do not sell to patients.
- Purity: 99.75%
- CAS No.: 868273-06-7
- Formula: C24H28ClN3O
- Molecular Weight:409.95
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Membrane Protein-targeted Compound Library
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Allosteric Modulators (AMs) Compound Library
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Biological Activity
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
83 nM
Compound: 1; Org27569
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Positive allosteric modulator activity at human CB1R expressed in CHO cells assessed as enhanced binding of [3H]CP55,940 after 60 mins by liquid scintillation spectrometric analysis
Positive allosteric modulator activity at human CB1R expressed in CHO cells assessed as enhanced binding of [3H]CP55,940 after 60 mins by liquid scintillation spectrometric analysis
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[PMID: 26529344] |
| CHO-K1 | EC50 |
324 nM
Compound: 1; Org27569
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Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as effect on CP55,940-induced inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by CP55,940 addition measured for 30 mins by HitHunte
Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as effect on CP55,940-induced inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by CP55,940 addition measured for 30 mins by HitHunte
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[PMID: 26529344] |
| CHO-K1 | EC50 |
9.05 nM
Compound: 1; Org27569
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Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as inhibition of CP55,940-induced beta-arrestin recruitment preincubated for 30 mins followed by CP55,940 addition measured for 90 mins by PathHunter assay
Negative allosteric modulator activity at human CB1R expressed in CHO-K1 cells assessed as inhibition of CP55,940-induced beta-arrestin recruitment preincubated for 30 mins followed by CP55,940 addition measured for 90 mins by PathHunter assay
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[PMID: 26529344] |
| CHO-K1 | IC50 |
2 nM
Compound: Org27569
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Negative allosteric modulation of human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP55940 induced beta arrestin recruitment preincubated for 30 mins followed by addition of CP55940 for 90 mins by chemiluminescence assay
Negative allosteric modulation of human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP55940 induced beta arrestin recruitment preincubated for 30 mins followed by addition of CP55940 for 90 mins by chemiluminescence assay
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[PMID: 27542310] |
| HEK293 | EC50 |
0.14 μM
Compound: 1, Org 27569
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Allosteric modulation of human recombinant CB1 receptor expressed in HEK293 cells assessed as stimulation of [3H]CP55940 binding
Allosteric modulation of human recombinant CB1 receptor expressed in HEK293 cells assessed as stimulation of [3H]CP55940 binding
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[PMID: 22571451] |
| HEK293 | EC50 |
0.64 μM
Compound: 1, ORG27569
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Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 15 mins in presence of CP55,940 by cAMP BRET assay
Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 15 mins in presence of CP55,940 by cAMP BRET assay
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[PMID: 26203658] |
| HEK293 | EC50 |
10.59 μM
Compound: 1, ORG27569
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Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 5 mins in presence of CP55,940 by cAMP BRET assay
Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 5 mins in presence of CP55,940 by cAMP BRET assay
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[PMID: 26203658] |
| HEK293 | EC50 |
2.09 μM
Compound: 1, ORG27569
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Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 10 mins in presence of CP55,940 by cAMP BRET assay
Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation after 10 mins in presence of CP55,940 by cAMP BRET assay
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[PMID: 26203658] |
| HEK293 | EC50 |
2.24 μM
Compound: 1, ORG27569
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Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation in presence of CP55,940 by cAMP BRET assay
Activity at hemagglutinin-tagged human CB1 receptor expressed in HEK293 cells assessed as effect on forskolin-induced cAMP accumulation in presence of CP55,940 by cAMP BRET assay
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[PMID: 26203658] |
| HEK293 | IC50 |
>10 μM
Compound: 1, Org 27569
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Allosteric modulation of human recombinant CB2 receptor expressed in HEK293 cells assessed as inhibition of [3H]CP55940 binding
Allosteric modulation of human recombinant CB2 receptor expressed in HEK293 cells assessed as inhibition of [3H]CP55940 binding
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[PMID: 22571451] |
Org 27569 enhances agonist (CP55940) binding, promotes agonist binding to CB1 yet inhibits agonist-induced G protein activation and blocks the agonist-induced conformational changes in TM6. Org 27569 inhibits agonist-induced TM6 movement in CB1 detected by a fluorescent probe on site 342[2]. Org 27569 produces a significant, but saturable, increase in the level of specific [3H]CP 55,940 binding. Org 27569 (1 μM) inhibits electrically evoked contractions of the mouse vas deferens with the pEC50 and Emax being 8.66±0.11 and 77% (95% confidence limits, 70.6-82.7), respectively[4]. In hCB1R cells, Org 27569 (1 and 10 μM) behaves as a weak inverse agonist producing a small but significant decrease in basal [35S]GTPγS binding. Org 27569 is less effective as an inhibitor of WIN55212-mediated inhibition of forskolin-stimulated cAMP production. Org 27569 induces a small but significant level of ERK1/2 phosphorylation with an Emax of 19% and pEC50 value of 8.55±0.99[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 868273-06-7
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Appearance Solid
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Molecular Weight 409.95
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Formula C24H28ClN3O
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Color Off-white to pink
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SMILES
ClC1=CC=C(C2=C1)NC(C(NCCC3=CC=C(C=C3)N4CCCCC4)=O)=C2CC
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvent & Solubility
DMSO : ≥ 52.2 mg/mL (127.33 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (6.10 mM); Suspended solution; Need ultrasonic
This protocol yields a suspended solution of 2.5 mg/mL. Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
Binding assays are performed with the CB1 receptor agonist [3H]CP 55,940 (0.7 nM) and the CB1 receptor antagonist [3H]SR 141716A (1.2 nM), 1 mg/mL BSA and 50 mM Tris buffer containing 0.1 mM EDTA and 0.5 mM MgCl2, pH 7.4, in a total assay volume of 500 μL. Binding is initiated by the addition of mouse brain membranes (30 μg). Assays are carried out at 37°C for 60 min before termination by addition of ice-cold wash buffer (50 mM Tris buffer and 1 mg/mL BSA) and vacuum filtration using a 24-well sampling manifold and Whatman GF/B glass-fiber filters that have been soaked in wash buffer at 4°C for 24 h. Each reaction tube is washed five times with a 4-mL aliquot of buffer. The filters are oven-dried for 60 min and then placed in 5 mL of scintillation fluid, and radioactivity is quantitated by liquid scintillation spectrometry. Specific binding is defined as the difference between the binding that occurs in the presence and absence of 1 μM concentrations of the corresponding unlabeled ligand and is 70 to 80% of the total binding.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Following a 1-week acclimation period, CB1 (+/+) and (−/−) mice are food-deprived, given an intraperitoneal injection of Org27569 (30 mg/kg), rimonabant (10 mg/kg; positive control), or vehicle at 23 h, and placed in a plastic cage with access to water. A premeasured amount (2.3-2.6 g) of sweet cereal or standard chow is placed in the test cage from 24 to 26h. All mice receive each treatment condition in a counterbalanced design, with at least 96 h between test days.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (276 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Jing L, et al. Effects of the cannabinoid CB? receptor allosteric modulator ORG 27569 on reinstatement of cocaine- and methamphetamine-seeking behavior in rats. Drug Alcohol Depend. 2014 Oct 1;143:251-6. [Content Brief]
[2]. Fay JF, et al. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569. J Biol Chem. 2012 Jul 30. [Content Brief]
[3]. Gamage TF, et al. In-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569. Behav Pharmacol. 2014 Apr;25(2):182-5. [Content Brief]
[4]. Price MR, et al. Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol. 2005 Nov;68(5):1484-95. [Content Brief]
[5]. Baillie GL, et al. CB(1) receptor allosteric modulators display both agonist and signaling pathway specificity. Mol Pharmacol. 2013 Feb;83(2):322-38. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.4393 mL | 12.1966 mL | 24.3932 mL | 60.9830 mL |
| 5 mM | 0.4879 mL | 2.4393 mL | 4.8786 mL | 12.1966 mL | |
| 10 mM | 0.2439 mL | 1.2197 mL | 2.4393 mL | 6.0983 mL | |
| 15 mM | 0.1626 mL | 0.8131 mL | 1.6262 mL | 4.0655 mL | |
| 20 mM | 0.1220 mL | 0.6098 mL | 1.2197 mL | 3.0492 mL | |
| 25 mM | 0.0976 mL | 0.4879 mL | 0.9757 mL | 2.4393 mL | |
| 30 mM | 0.0813 mL | 0.4066 mL | 0.8131 mL | 2.0328 mL | |
| 40 mM | 0.0610 mL | 0.3049 mL | 0.6098 mL | 1.5246 mL | |
| 50 mM | 0.0488 mL | 0.2439 mL | 0.4879 mL | 1.2197 mL | |
| 60 mM | 0.0407 mL | 0.2033 mL | 0.4066 mL | 1.0164 mL | |
| 80 mM | 0.0305 mL | 0.1525 mL | 0.3049 mL | 0.7623 mL | |
| 100 mM | 0.0244 mL | 0.1220 mL | 0.2439 mL | 0.6098 mL |
Org 27569 Related Classifications
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