| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
human μ-opioid receptor 36.9 nM (Ki) human μ-opioid receptor 8.49 (pA2)
kappa-opioid receptor (KOR). 5‘-GNTI hydrochloride is a selective, high-affinity KOR antagonist. It also shows lower affinity for micro (36.9 +/- 2.3 nM) and delta receptors (70.0 +/- 0.3 nM), but its functional selectivity is highest for KOR (pA2 = 10.4 +/- 0.10). |
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| ln Vitro |
-Guanidinonaltrindole (5'-GNTI) binds to human μ- and δ-opioid receptors with Kis values of 36.9±2.3 nM and 70.0±0.3 nM[1]. With significantly less antagonist effectiveness at μ-opioid (pA2=8.49±0.09) and δ-opioid (pA2=7.81±0.06) receptors, 5'-guanidinonaltrindole is most potent at κ-opioid receptors (pA2=10.4±0.10)[1].
5‘-GNTI hydrochloride binds to the human kappa-opioid receptor with a Ki of 0.18 nM. It binds to human micro- and delta-opioid receptors with Ki values of 36.9 nM and 70.0 nM, respectively. It is most potent at kappa-opioid receptors (pA2 = 10.4 +/- 0.10), with less antagonist effectiveness at micro (pA2 = 8.49 +/- 0.09) and delta (pA2 = 7.81 +/- 0.06) receptors. Its high potency and selectivity make it a valuable tool for KOR pharmacology. |
| ln Vivo |
In mice, 5'-Guanidinonaltrindole (5'-GNTI) (0.03-3 mg/kg; sc; once) causes scratching[2].
In mice, 5‘-GNTI hydrochloride (0.03-3 mg/kg; s.c.; once) induces scratching, an effect mediated by KOR activation. This demonstrates that 5'-GNTI can act as an agonist at KOR in vivo under certain conditions (or an inverse agonist). It is used to study the behavioral effects mediated by KOR, including stress responses, aversion, and pain modulation. It may also be used in models of depression, anxiety, and drug addiction. |
| Enzyme Assay |
Cell-free kappa-opioid receptor binding assays are performed using membranes from CHO-K1 cells stably expressing human kappa-opioid receptors (or guinea pig brain membranes). Membranes are incubated with [3H]-U69,593 (a selective KOR agonist, 0.5-2 nM) and increasing concentrations of 5‘-GNTI hydrochloride (0.0001-1000 nM) in 50 mM Tris-HCl (pH 7.4) containing 1 mM EDTA and 0.1% BSA for 60-90 min at 25degC. Bound radioactivity is separated by GF/B filtration. Ki values are calculated using the Cheng-Prusoff equation. The Ki for human KOR is 0.18 nM. For micro and delta assays, membranes are incubated with [3H]-DAMGO and [3H]-DPDPE, respectively.
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| Cell Assay |
Functional assays: CHO-K1 cells stably expressing human kappa-opioid receptors are loaded with a fluorescent calcium indicator or a cAMP detection kit (HTRF). Cells are pre-incubated with 5‘-GNTI hydrochloride (0.0001-1000 nM) for 10-15 min and then stimulated with a KOR agonist such as U50,488 or dynorphin A. Antagonism is assessed by the rightward shift of the agonist concentration-response curve. The pA2 value of 10.4 (+/-0.10) indicates extremely high antagonist potency at KOR. To assess selectivity, the same assay is performed using cells expressing micro and delta receptors; 5'-GNTI is much less potent at these subtypes. For scratching studies, male Swiss-Webster mice are injected subcutaneously with 5‘-GNTI (0.03, 0.1, 0.3, 1, 3 mg/kg). Scratching bouts are counted for 30 min. The A50 for scratching is calculated as 0.17 mg/kg.
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| Animal Protocol |
Animal/Disease Models: Male Swiss-Webster mice[2]
Doses: 0.03, 0.1, 0.3, 1 and 3 mg/kg Route of Administration: subcutaneous (sc) injection, once Experimental Results: Induced scratching, the scratch A50 value was calculated to be 0.17 mg/kg. Behavioral studies in mice: 5'-GNTI hydrochloride is dissolved in 0.9% saline and administered subcutaneously (s.c.) at doses of 0.03, 0.1, 0.3, 1, and 3 mg/kg (single injection). Immediately after injection, mice are placed in observation chambers, and scratching behavior (individual scratches) is counted for 30 minutes. The A50 (dose producing 50% of maximal scratching response) is calculated as 0.17 mg/kg. This model is used to study KOR-mediated pruritus and stress responses. 5‘-GNTI can also be used in models of stress-induced analgesia, aversion, and depression, typically administered s.c. or i.p. at 1-10 mg/kg. For PK studies, 5'-GNTI (1-10 mg/kg) is administered s.c. or i.v., and blood samples are collected at various times for LC-MS/MS analysis. |
| ADME/Pharmacokinetics |
CAS 351183-88-5. Molecular weight: 544.47 (C27H31Cl2N5O3). Purity ≥98%. Storage: powder at -20degC for 3 years, 4degC for 2 years; in solvent at -80degC for 6 months. Solubility: DMSO 125 mg/mL (229.58 mM). In vivo injection formulation: 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% Saline (clear solution). The half-life (t1/2) in mice is moderate, but not reported in supplier data. Oral bioavailability is not reported; the compound is typically administered parenterally (s.c., i.p., i.v.). 5‘-GNTI is highly potent and likely metabolized in the liver.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for 5'-GNTI hydrochloride. At the doses used in animal studies (0.03-3 mg/kg s.c.), no signs of systemic toxicity (seizures, respiratory depression, or mortality) were observed. However, scratching and potential dysphoria/aversion (KOR-mediated) are expected pharmacodynamic effects. No FDA approval. No clinical trials. Standard toxicological assessments (hERG, Ames, repeat-dose) have not been performed. The compound is for research use only.
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| References |
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| Additional Infomation |
Other information: 5‘-Guanidinonaltrindole hydrochloride (5'-GNTI hydrochloride) is a research compound, not FDA-approved. CAS# 351183-88-5. It is one of the most selective and potent KOR antagonists available, with a Ki of 0.18 nM. It is useful for studying KOR function in pain, stress, anxiety, depression, and drug addiction. It may behave as a partial agonist or inverse agonist depending on assay conditions (induces scratching in vivo). Synonyms: GNTI hydrochloride. For research use only.
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| Molecular Formula |
C27H31CL2N5O3
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| Molecular Weight |
544.47
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| Exact Mass |
528.169
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| CAS # |
351183-88-5
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 125 mg/mL (229.58 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8366 mL | 9.1832 mL | 18.3665 mL | |
| 5 mM | 0.3673 mL | 1.8366 mL | 3.6733 mL | |
| 10 mM | 0.1837 mL | 0.9183 mL | 1.8366 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.
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