ORG-27569 - CAS 868273-06-7
Catalog number: 868273-06-7
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C24H28ClN3O
Molecular Weight:
409.95
COA:
Inquire
Targets:
Cannabinoid Receptor
Description:
Org 27569 is an allosteric modulator of cannabinoid CB1 receptor, induces a CB1 receptor state that is characterized by enhanced agonist affinity and decreased inverse agonist affinity.
Purity:
0.98
Synonyms:
ORG-27569; ORG-27569; ORG-27569.
MSDS:
Inquire
InChIKey:
AHFZDNYNXFMRFQ-UHFFFAOYSA-N
InChI:
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)
Canonical SMILES:
CCC1=C(NC2=C1C=C(C=C2)Cl)C(=O)NCCC3=CC=C(C=C3)N4CCCCC4
1.Optimization of chemical functionalities of indole-2-carboxamides to improve allosteric parameters for the cannabinoid receptor 1 (CB1).
Khurana L;Ali HI;Olszewska T;Ahn KH;Damaraju A;Kendall DA;Lu D J Med Chem. 2014 Apr 10;57(7):3040-52. doi: 10.1021/jm5000112. Epub 2014 Mar 27.
5-Chloro-3-ethyl-N-(4-(piperidin-1-yl)phenethyl)-1H-indole-2-carboxamide (1; ORG27569) is a prototypical allosteric modulator for the cannabinoid type 1 receptor (CB1). Here, we reveal key structural requirements of indole-2-carboxamides for allosteric modulation of CB1: a critical chain length at the C3-position, an electron withdrawing group at the C5-position, the length of the linker between the amide bond and the phenyl ring B, and the amino substituent on the phenyl ring B. These significantly impact the binding affinity (KB) and the binding cooperativity (α). A potent CB1 allosteric modulator 5-chloro-N-(4-(dimethylamino)phenethyl)-3-propyl-1H-indole-2-carboxamide (12d) was identified. It exhibited a KB of 259.3 nM with a strikingly high binding α of 24.5. We also identified 5-chloro-N-(4-(dimethylamino)phenethyl)-3-hexyl-1H-indole-2-carboxamide (12f) with a KB of 89.1 nM, which is among the lowest KB values obtained for any allosteric modulator of CB1. These positive allosteric modulators of orthosteric agonist binding nonetheless antagonized the agonist-induced G-protein coupling to the CB1 receptor, yet induced β-arrestin mediated ERK1/2 phosphorylation.
2.Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors.
Tham M;Yilmaz O;Alaverdashvili M;Kelly MEM;Denovan-Wright EM;Laprairie RB Br J Pharmacol. 2018 Jul 7. doi: 10.1111/bph.14440. [Epub ahead of print]
BACKGROUND AND PURPOSE: ;We sought to understand why (-)-cannabidiol (CBD) and (-)-cannabidiol-dimethylheptyl (CBD-DMH) exhibit distinct pharmacology, despite near identical structures.;EXPERIMENTAL APPROACH: ;HEK293A cells expressing either human type 1 cannabinoid (CB;1; ) receptors or CB;2; receptors were treated with CBD or CBD-DMH with or without the CB;1; and CB;2; receptor agonist CP55,940, CB;1; receptor allosteric modulator Org27569 or CB;2; receptor inverse agonist SR144528. Ligand binding, cAMP levels and βarrestin1 recruitment were measured. CBD and CBD-DMH binding was simulated with models of human CB;1; or CB;2; receptors, based on the recently published crystal structures of agonist-bound (5XRA) or antagonist-bound (5TGZ) human CB;1; receptors.;KEY RESULTS: ;At CB;1; receptors, CBD was a negative allosteric modulator (NAM), and CBD-DMH was a mixed agonist/positive allosteric modulator. CBD and Org27569 shared multiple interacting residues in the antagonist-bound model of CB;1; receptors (5TGZ) but shared a binding site with CP55,940 in the agonist-bound model of CB;1; receptors (5XRA). The binding site for CBD-DMH in the CB;1; receptor models overlapped with CP55,940 and Org27569.
3.Effects of the cannabinoid CB₁ receptor allosteric modulator ORG 27569 on reinstatement of cocaine- and methamphetamine-seeking behavior in rats.
Jing L;Qiu Y;Zhang Y;Li JX Drug Alcohol Depend. 2014 Oct 1;143:251-6. doi: 10.1016/j.drugalcdep.2014.08.004. Epub 2014 Aug 17.
BACKGROUND: ;Cannabinoid CB1 receptors play an essential role in drug addiction. Given the side effect profiles of orthosteric CB1 antagonism, new strategies have been attempted to modulate this target, such as CB1 receptor allosteric modulation. However, the effect of CB1 allosteric modulation in drug addiction is unknown. The present study examined the effects of the CB1 receptor allosteric modulator ORG27569 on the reinstatement of cocaine- and methamphetamine-seeking behavior in rats.;METHODS: ;Rats were trained to self-administer 0.75 mg/kg cocaine or 0.05 mg/kg methamphetamine in 2-h daily sessions for 14 days which was followed by 7 days of extinction sessions in which rats responded on the levers with no programmed consequences. 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.).;RESULTS: ;Both cues and a priming injection of cocaine or methamphetamine significantly reinstated the extinguished active lever responding. Pretreatment with ORG27569 resulted in a dose-related attenuation of both cue- and drug-induced reinstatement of cocaine- and methamphetamine-seeking behavior.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related Cannabinoid Receptor Products


CAS 851728-60-4 PF 514273

PF 514273
(CAS: 851728-60-4)

PF 514273 is a novel, bicyclic lactam-based cannabinoid-1 receptor antagonist for the treatment of obesity. The Ki for binding to CB1 and CB2 receptors is 1 nM ...

CAS 111-57-9 Stearoyl ethanolamide

Stearoyl ethanolamide
(CAS: 111-57-9)

Stearoyl ethanolamide is the ethanolamide of octadecanoic acid and an endocannabinoid neurotransmitter. It exhibits anorexic activity in mice.<br/>Nutritional s...

CAS 1314035-51-2 Hemopressin (human, mouse)

Hemopressin (human, mouse)
(CAS: 1314035-51-2)

Hemopressin (human, mouse) is a bioactive endogenous peptide substrate for endopeptidase 24.15, neurolysin and ACE (Ki = 27.76, 3.43 and 1.87 μM, respectively)....

CAS 259869-55-1 JWH 133

JWH 133
(CAS: 259869-55-1)

JWH 133 is a synthetic cannabinoid and acts as a potent CB2 selective agonist with Ki value of 3.4 nM. It is used to synthesize CB2-selective cannabinoid recept...

CAS 959746-77-1 A-836339

A-836339
(CAS: 959746-77-1)

A-836339 is a synthetic and potent cannabinoid receptor full agonist. It displays a higher affinity for the peripheral CB2 receptor with Ki value of 0.64 nM ove...

CAS 251908-92-6 AM 1172

AM 1172
(CAS: 251908-92-6)

AM 1172, an AEA analogue, has been found to be an anandamide uptake inhibitor as well as a cannabinoid receptor partial agonist.

CAS 1446-61-3 Leelamine

Leelamine
(CAS: 1446-61-3)

Leelamine, a diterpene molecule, has weak affinity for the human central cannabinoid (CB1) and peripheral cannabinoid (CB2) receptors. Leelamine is also a PDK(p...

CAS 362519-49-1 Slv319

Slv319
(CAS: 362519-49-1)

Slv319 is a potent antagonist of CB1 recceptor (Ki = 7.8 nM) used for the treatment of neuroinflammatory disorders, cognitive disorders, septic shock, obesity, ...

Chemical Structure

CAS 868273-06-7 ORG-27569

Quick Inquiry

Verification code

Featured Items