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MedKoo Cat#: 510212 | Name: ORG-27569
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

ORG-27569 is a drug which acts as a potent and selective allosteric modulator of the cannabinoid CB1 receptor. Studies in vitro suggest that it binds to a regulatory site on the CB1 receptor target, causing a conformational change that increases the binding affinity of CB1 agonists such as CP 55,940, while decreasing the binding affinity of CB1 antagonists or inverse agonists such as rimonabant. However while Org 27569 increases the ability of CB1 agonists to bind to the receptor, it decreases their efficacy at stimulating second messenger signalling once bound, and so in practice behaves as an insurmountable antagonist of CB1 receptor function.

Chemical Structure

ORG-27569
ORG-27569
CAS#868273-06-7

Theoretical Analysis

MedKoo Cat#: 510212

Name: ORG-27569

CAS#: 868273-06-7

Chemical Formula: C24H28ClN3O

Exact Mass: 409.1921

Molecular Weight: 409.96

Elemental Analysis: C, 70.31; H, 6.88; Cl, 8.65; N, 10.25; O, 3.90

Price and Availability

Size Price Availability Quantity
10mg USD 550.00 2 Weeks
50mg USD 1,450.00 2 Weeks
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Related CAS #
No Data
Synonym
ORG27569; ORG-27569; ORG 27569.
IUPAC/Chemical Name
5-chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide
InChi Key
AHFZDNYNXFMRFQ-UHFFFAOYSA-N
InChi Code
InChI=1S/C24H28ClN3O/c1-2-20-21-16-18(25)8-11-22(21)27-23(20)24(29)26-13-12-17-6-9-19(10-7-17)28-14-4-3-5-15-28/h6-11,16,27H,2-5,12-15H2,1H3,(H,26,29)
SMILES Code
O=C(C(N1)=C(CC)C2=C1C=CC(Cl)=C2)NCCC3=CC=C(N4CCCCC4)C=C3
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>5 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
         
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Org 27569 is a potent CB1 receptor allosteric modulator.
In vitro activity:
An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here this study explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. These results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation. Reference: J Biol Chem. 2012 Sep 28;287(40):33873-82. https://pubmed.ncbi.nlm.nih.gov/22846992/
In vivo activity:
On reinstatement test sessions, rats were administered ORG27569 (1.0, 3.2, 5.6 mg/kg, i.p.) or SR141716A (3.2 mg/kg, i.p.) 10 min prior to re-exposure to cocaine- or methamphetamine-paired cues or a priming injection of cocaine (10mg/kg, i.p.) or methamphetamine (1mg/kg, i.p.). Pretreatment with ORG27569 resulted in a dose-related attenuation of both cue- and drug-induced reinstatement of cocaine- and methamphetamine-seeking behavior. Reference: Drug Alcohol Depend. 2014 Oct 1;143:251-6. https://pubmed.ncbi.nlm.nih.gov/25169627/
Solvent mg/mL mM
Solubility
DMSO 58.4 142.45
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 409.96 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Fay JF, Farrens DL. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569. J Biol Chem. 2012 Sep 28;287(40):33873-82. doi: 10.1074/jbc.M112.352328. Epub 2012 Jul 30. PMID: 22846992; PMCID: PMC3460482. 2. Ahn KH, Mahmoud MM, Kendall DA. Allosteric modulator ORG27569 induces CB1 cannabinoid receptor high affinity agonist binding state, receptor internalization, and Gi protein-independent ERK1/2 kinase activation. J Biol Chem. 2012 Apr 6;287(15):12070-82. doi: 10.1074/jbc.M111.316463. Epub 2012 Feb 16. PMID: 22343625; PMCID: PMC3320953. 3. Jing L, Qiu Y, Zhang Y, Li JX. Effects of the cannabinoid CB₁ receptor allosteric modulator ORG 27569 on reinstatement of cocaine- and methamphetamine-seeking behavior in rats. Drug Alcohol Depend. 2014 Oct 1;143:251-6. doi: 10.1016/j.drugalcdep.2014.08.004. Epub 2014 Aug 17. PMID: 25169627; PMCID: PMC4161648. 4. Gamage TF, Ignatowska-Jankowska BM, Wiley JL, Abdelrahman M, Trembleau L, Greig IR, Thakur GA, Tichkule R, Poklis J, Ross RA, Pertwee RG, Lichtman AH. In-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569. Behav Pharmacol. 2014 Apr;25(2):182-5. doi: 10.1097/FBP.0000000000000027. PMID: 24603340; PMCID: PMC4042670.
In vitro protocol:
1. Fay JF, Farrens DL. A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569. J Biol Chem. 2012 Sep 28;287(40):33873-82. doi: 10.1074/jbc.M112.352328. Epub 2012 Jul 30. PMID: 22846992; PMCID: PMC3460482. 2. Ahn KH, Mahmoud MM, Kendall DA. Allosteric modulator ORG27569 induces CB1 cannabinoid receptor high affinity agonist binding state, receptor internalization, and Gi protein-independent ERK1/2 kinase activation. J Biol Chem. 2012 Apr 6;287(15):12070-82. doi: 10.1074/jbc.M111.316463. Epub 2012 Feb 16. PMID: 22343625; PMCID: PMC3320953.
In vivo protocol:
1. Jing L, Qiu Y, Zhang Y, Li JX. Effects of the cannabinoid CB₁ receptor allosteric modulator ORG 27569 on reinstatement of cocaine- and methamphetamine-seeking behavior in rats. Drug Alcohol Depend. 2014 Oct 1;143:251-6. doi: 10.1016/j.drugalcdep.2014.08.004. Epub 2014 Aug 17. PMID: 25169627; PMCID: PMC4161648. 2. Gamage TF, Ignatowska-Jankowska BM, Wiley JL, Abdelrahman M, Trembleau L, Greig IR, Thakur GA, Tichkule R, Poklis J, Ross RA, Pertwee RG, Lichtman AH. In-vivo pharmacological evaluation of the CB1-receptor allosteric modulator Org-27569. Behav Pharmacol. 2014 Apr;25(2):182-5. doi: 10.1097/FBP.0000000000000027. PMID: 24603340; PMCID: PMC4042670.
1: Nations KR, Dogterom P, Bursi R, Schipper J, Greenwald S, Zraket D, Gertsik L, Johnstone J, Lee A, Pande Y, Ruigt G, Ereshefsky L. Examination of Org 26576, an AMPA receptor positive allosteric modulator, in patients diagnosed with major depressive disorder: an exploratory, randomized, double-blind, placebo- controlled trial. J Psychopharmacol. 2012 Dec;26(12):1525-39. doi: 10.1177/0269881112458728. Epub 2012 Sep 6. PMID: 22954616. 2: Nations KR, Bursi R, Dogterom P, Ereshefsky L, Gertsik L, Mant T, Schipper J. Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection. Drugs R D. 2012 Sep 1;12(3):127-39. doi: 10.2165/11634360-000000000-00000. PMID: 22852579; PMCID: PMC3585695. 3: Adler LA, Kroon RA, Stein M, Shahid M, Tarazi FI, Szegedi A, Schipper J, Cazorla P. A translational approach to evaluate the efficacy and safety of the novel AMPA receptor positive allosteric modulator org 26576 in adult attention- deficit/hyperactivity disorder. Biol Psychiatry. 2012 Dec 1;72(11):971-7. doi: 10.1016/j.biopsych.2012.05.012. Epub 2012 Jul 6. PMID: 22771238. 4: Fumagalli F, Calabrese F, Luoni A, Shahid M, Racagni G, Riva MA. The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus. Pharmacol Res. 2012 Feb;65(2):176-81. doi: 10.1016/j.phrs.2011.10.004. Epub 2011 Nov 3. PMID: 22079295. 5: Jardemark K, Marcus MM, Malmerfelt A, Shahid M, Svensson TH. Differential effects of AMPA receptor potentiators and glycine reuptake inhibitors on antipsychotic efficacy and prefrontal glutamatergic transmission. Psychopharmacology (Berl). 2012 May;221(1):115-31. doi: 10.1007/s00213-011-2554-3. Epub 2011 Nov 9. PMID: 22068461. 6: Bursi R, Erdemli G, Campbell R, Hutmacher MM, Kerbusch T, Spanswick D, Jeggo R, Nations KR, Dogterom P, Schipper J, Shahid M. Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576. Psychopharmacology (Berl). 2011 Dec;218(4):713-24. doi: 10.1007/s00213-011-2365-6. Epub 2011 Jun 7. PMID: 21647578. 7: Hamlyn E, Brand L, Shahid M, Harvey BH. The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats. Behav Pharmacol. 2009 Oct;20(7):662-7. doi: 10.1097/FBP.0b013e328331ba1b. PMID: 19741506. 8: Su XW, Li XY, Banasr M, Koo JW, Shahid M, Henry B, Duman RS. Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus. Psychopharmacology (Berl). 2009 Oct;206(2):215-22. doi: 10.1007/s00213-009-1598-0. Epub 2009 Jul 15. PMID: 19603152. 9: Dawson N, Ferrington L, Olverman HJ, Kelly PA. Novel analysis for improved validity in semi-quantitative 2-deoxyglucose autoradiographic imaging. J Neurosci Methods. 2008 Oct 30;175(1):25-35. doi: 10.1016/j.jneumeth.2008.07.020. Epub 2008 Aug 12. PMID: 18762213. 10: Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K. Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by 14C-2-deoxyglucose autoradiography. Neuropharmacology. 2005 Aug;49(2):254-64. doi: 10.1016/j.neuropharm.2005.03.011. PMID: 15993447.