| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
GR 89696 targets the κ-opioid receptor (KOR) as a selective antagonist. It binds with high affinity to KOR, blocking the effects of endogenous dynorphins and other KOR agonists. By antagonizing KOR, GR 89696 modulates pain perception, stress responses, and reward pathways. The compound has been used to study the role of KOR in addiction, depression, anxiety, and pain modulation, as well as to differentiate KOR-mediated effects from those mediated by μ- and δ-opioid receptors.
|
|---|---|
| ln Vitro |
In vitro, GR 89696 demonstrates high affinity binding to κ-opioid receptors in radioligand binding assays. It effectively blocks KOR activation by agonists such as dynorphin A, inhibiting downstream signaling pathways including G-protein activation, inhibition of adenylate cyclase, and MAPK signaling. The compound has been used in functional assays to characterize the pharmacological profile of KOR and to differentiate its roles from other opioid receptor subtypes.
|
| ln Vivo |
In a dose-dependent way, GR 89696 (intramuscular injection, 0.01-0.1 μg/kg) can reduce the scratch reaction brought on by intrathecal morphine (0.03 mg) without impairing the analgesic effect of the drug [1]. using an arterial inertial ischemia model, an infusion of 1 mg/kg decreased the amount of the cerebral artery infarct by 38% [2].
In vivo, GR 89696 has been used in animal models to investigate the role of KOR in pain, stress, addiction, and depression. It modulates KOR-mediated behaviors including stress-induced analgesia, dysphoria, and aversive responses. The compound has been instrumental in understanding the role of the dynorphin/KOR system in stress-related psychiatric disorders and in the development of KOR antagonists as potential therapeutics for depression and addiction. |
| Enzyme Assay |
Radioligand binding assays: Membranes from cells expressing κ-opioid receptors (or brain tissue preparations) are incubated with a radiolabeled KOR ligand (e.g., [³H]-U69,593) and GR 89696 at various concentrations (typically 0.1-100 nM). Binding affinity (Kᵢ) is calculated from displacement curves. Selectivity is assessed by testing against μ- and δ-opioid receptors.
|
| Cell Assay |
Cells expressing recombinant κ-opioid receptors (e.g., CHO or HEK293 cells) are cultured in appropriate media. For functional assays, cells are pre-incubated with GR 89696 and then stimulated with a KOR agonist such as dynorphin A or U69,593. Receptor activation is assessed by measuring inhibition of forskolin-stimulated cAMP accumulation using ELISA or HTRF-based detection kits, or by measuring G-protein activation using [³⁵S]GTPγS binding assays. IC₅₀ values are calculated from dose-response curves.
|
| Animal Protocol |
In vivo studies are conducted in rodent models. GR 89696 is administered via intraperitoneal, subcutaneous, or intracerebroventricular injection at specified doses. Behavioral tests (e.g., forced swim test for depression, elevated plus maze for anxiety, tail flick for analgesia, and conditioned place aversion for aversive responses) are performed. Stress responses are evaluated in relevant models. Neurochemical measurements are performed using microdialysis or tissue analysis.
|
| ADME/Pharmacokinetics |
GR 89696 fumarate is a selective κ-opioid receptor antagonist with high affinity (Kᵢ values typically in the low nanomolar range). It is soluble in DMSO and other organic solvents. The compound is stable under recommended storage conditions and is suitable for both in vitro and in vivo pharmacological research. Detailed physicochemical properties are available from chemical suppliers.
|
| References |
|
| Additional Infomation |
See also: GR 89696 (Note moved to).
GR 89696 fumarate is a selective antagonist of the κ-opioid receptor (KOR). It has been used in pharmacological research to study the role of KOR in pain modulation, stress responses, addiction, and neuropsychiatric disorders. The compound has been instrumental in understanding the dynorphin/KOR system and in the development of KOR antagonists as potential therapeutics for depression, anxiety, and addiction. |
| Molecular Formula |
C19H25N3O3CL2.C4H4O4
|
|---|---|
| Molecular Weight |
530.39826
|
| Exact Mass |
529.138
|
| CAS # |
126766-32-3
|
| Related CAS # |
GR 89696 free base;126766-31-2
|
| PubChem CID |
6442840
|
| Appearance |
White to off-white solid powder
|
| Boiling Point |
559.2ºC at 760 mmHg
|
| Flash Point |
292ºC
|
| Vapour Pressure |
1.55E-12mmHg at 25°C
|
| LogP |
2.436
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
35
|
| Complexity |
649
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
COC(=O)N1CCN(C(C1)CN2CCCC2)C(=O)CC3=CC(=C(C=C3)Cl)Cl.C(=C/C(=O)O)\C(=O)O
|
| InChi Key |
ABTNETSDXZBJTE-WLHGVMLRSA-N
|
| InChi Code |
InChI=1S/C19H25Cl2N3O3.C4H4O4/c1-27-19(26)23-8-9-24(15(13-23)12-22-6-2-3-7-22)18(25)11-14-4-5-16(20)17(21)10-14;5-3(6)1-2-4(7)8/h4-5,10,15H,2-3,6-9,11-13H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1+
|
| Chemical Name |
(E)-but-2-enedioic acid;methyl 4-[2-(3,4-dichlorophenyl)acetyl]-3-(pyrrolidin-1-ylmethyl)piperazine-1-carboxylate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 50 mg/mL (~94.27 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8854 mL | 9.4268 mL | 18.8537 mL | |
| 5 mM | 0.3771 mL | 1.8854 mL | 3.7707 mL | |
| 10 mM | 0.1885 mL | 0.9427 mL | 1.8854 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
