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Org 27569
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Org 27569图片
CAS NO:868273-06-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)409.95
FormulaC24H28ClN3O
CAS No.868273-06-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 82 mg/mL (200.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILESO=C(C(N1)=C(CC)C2=C1C=CC(Cl)=C2)NCCC3=CC=C(N4CCCCC4)C=C3
SynonymsORG27569; ORG-27569; ORG 27569
实验参考方法
In Vitro

In vitro activity: Org 27569 is an allosteric modulator of CB1 cannabinoid receptor. It significantly increases the binding of CB1 receptor agonist and causes a significant decrease in specific binding of CB1 receptor inverse agonist. Org 27569 induces CB1 high affinity agonist binding, receptor internalization, and downstream ERK phosphorylation. The allosteric ligand Org 27569 promotes agonist binding to CB1, yet blocks the agonist-induced conformational changes in TM6. Org 27569 traps the receptor in a distinct agonist-bound, but nonsignaling conformational state.


Kinase Assay: 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 occurred in the presence and absence of 1 μM concentrations of the corresponding unlabeled ligand and is 70 to 80% of the total binding.


Cell Assay: Cells expressing CB1 receptors are exposed to ORG27569 (10 μM) for 5 to 15 min. For toxin treatment to abrogate Gi coupling effects, PTX is added to the medium at 5 ng/ml. Following an 18-h incubation in the presence of toxin, cells are washed twice with PBS and treated with compounds. Cells are washed with ice-cold PBS, and cell lysates are obtained by harvesting the cells with ice-cold lysis buffer (150 mM NaCl, 1.0% IGEPAL CA-630, 0.5% sodium deoxycholate, 0.1% SDS, and 50 mM Tris, pH 7.5 containing 4-(2-aminoethyl)benzenesulfonyl fluoride, pepstatin A, E-64, bestatin, leupeptin, and aprotinin as protease inhibitors).

In VivoOrg 27569 has shown the potent inhibition of electrically evoked contractions of the mouse vas deferens by WIN55212 with the pEC50 and Emax of 8.24 ±0.12 and 45.4%, respectively.
Animal modelMice
Formulation & DosageFollowing 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.
References

Mol Pharmacol. 2005 Nov;68(5):1484-95; J Biol Chem. 2012 Apr 6;287(15):12070-82.