![[Des-His1,Glu9]-Glucagon amide TFA](/upload/1124/V77345.png)
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
glucagon receptor[1]
Glucagon receptor (GCGR), a class B G-protein-coupled receptor primarily expressed in the liver and pancreas. [Des-His1,Glu9]-Glucagon amide acts as a competitive antagonist, binding to the GCGR without activating it. This blocks the binding of endogenous glucagon, preventing the receptor-mediated activation of adenylate cyclase and the subsequent increase in intracellular cAMP, which normally leads to hepatic glucose production (glycogenolysis and gluconeogenesis). |
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| ln Vitro |
In vitro, [Des-His1,Glu9]-Glucagon amide TFA is a potent glucagon receptor antagonist with a pA2 value of 7.2 (pA2 is a measure of competitive antagonism; 7.2 corresponds to an apparent dissociation constant Kb of approximately 63 nM). In cell-based assays, it effectively blocks glucagon-induced cAMP accumulation in a concentration-dependent manner without exhibiting any intrinsic agonist activity, even at high concentrations. This makes it a pure competitive antagonist.
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| ln Vivo |
In animal models of diabetes, the glucagon receptor antagonist is used to suppress the effects of glucagon. By blocking the GCGR, it reduces hepatic glucose output, leading to lowered blood glucose levels. It has been shown to improve hyperglycemia in diabetic rodent models and is a valuable tool for studying the pathogenic role of glucagon in diabetes. It is potentially useful in the study of the pathogenesis of diabetes and for validating GCGR as a therapeutic target.
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| Enzyme Assay |
A non-cell competitive radioligand binding assay is performed to determine receptor binding affinity. Membranes from cells expressing the human glucagon receptor (e.g., CHO-GCGR) are incubated with the radioligand [125I]-glucagon (50-100 pM) in the presence of varying concentrations of the test antagonist. After incubation for 60-90 minutes at room temperature, bound and free radioligand are separated by filtration through GF/C filters. The radioactivity is counted, and the IC50 is calculated. The Ki is derived from the IC50 using the Cheng-Prusoff equation.
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| Cell Assay |
A functional cAMP accumulation assay is used to confirm antagonism. Cells expressing GCGR (e.g., HEK-293-GCGR) are seeded in 96-well plates and pre-treated with varying concentrations of the antagonist (0.1-1000 nM) for 15 minutes. The cells are then stimulated with a submaximal concentration of glucagon (e.g., 1-10 nM) in the presence of 0.5 mM IBMX. After 30-60 minutes, cAMP levels are measured using a homogeneous time-resolved fluorescence (HTRF) or ELISA-based kit. The antagonist causes a concentration-dependent rightward shift of the glucagon dose-response curve. The pA2 value (7.2) is calculated via Schild regression.
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| Animal Protocol |
In vivo efficacy is evaluated in db/db or STZ-induced diabetic mouse models. Animals are fasted for 4-6 hours and then administered [Des-His1,Glu9]-Glucagon amide TFA via intravenous (IV) or intraperitoneal (IP) injection at doses ranging from 0.1-5 mg/kg. Blood glucose levels are measured at 0, 15, 30, 60, 120, and 240 minutes post-injection using a glucometer. To confirm target engagement, glucagon (30-100 ug/kg) is co-administered, and the reduction in glucagon-stimulated glucose excursion is measured compared to the glucagon-only control group.
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| ADME/Pharmacokinetics |
As a peptide antagonist, [Des-His1,Glu9]-Glucagon amide TFA has low oral bioavailability and is typically administered via IV or IP injection. The C-terminal amidation and the modifications at positions 1 and 9 improve its stability against proteolytic degradation compared to native glucagon, resulting in a prolonged duration of action. However, the plasma half-life is still relatively short (30-60 minutes). The TFA salt is water-soluble, making it easy to formulate in saline or PBS. Storage: lyophilized powder at -80degC.
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| Toxicity/Toxicokinetics |
Toxicity data specific to [Des-His1,Glu9]-Glucagon amide TFA is not publicly available. As a peptide antagonist of GCGR, its pharmacology is well-tolerated in animal studies at the doses used (up to 5 mg/kg). Glucagon receptor antagonism reduces blood glucose and may lead to compensatory hyperglucagonemia, but no overt systemic toxicity or hepatotoxicity has been reported. The TFA salt is non-toxic. No clinical toxicology data exists as this is a research tool.
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| References | |
| Additional Infomation |
[Des-His1,Glu9]-Glucagon amide TFA is a research-grade chemical tool, not a drug. It has been used in seminal studies of diabetes pathogenesis (Unson CG, et al., Peptides, 1989). It is the standard reference antagonist for studying glucagon receptor pharmacology and for validating the potential of GCGR antagonism as a therapeutic strategy for type 2 diabetes. This product is for research use only (RUO) and has no FDA approval for human therapy.
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| Molecular Formula |
C150H222F3N41O49S
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| Molecular Weight |
3472.67
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| Related CAS # |
[Des-His1,Glu9]-Glucagon amide;110084-95-2
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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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2880 mL | 1.4398 mL | 2.8796 mL | |
| 5 mM | 0.0576 mL | 0.2880 mL | 0.5759 mL | |
| 10 mM | 0.0288 mL | 0.1440 mL | 0.2880 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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