| Targets |
EC50: 0.57 nM (GLP-1R), 0.75 nM (GIPR)
GLP‑1R/GIPR agonist‑1 targets the glucagon‑like peptide‑1 receptor (GLP‑1R) and the glucose‑dependent insulinotropic polypeptide receptor (GIPR), both of which are G protein‑coupled receptors (GPCRs) expressed on pancreatic beta‑cells, as well as in the brain, gut, and other tissues. Activation of GLP‑1R enhances glucose‑dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite. Activation of GIPR also enhances insulin secretion and may have additional metabolic benefits. Dual agonism of GLP‑1R and GIPR has been shown to be more effective than GLP‑1R agonism alone for glycemic control and weight loss. |
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| ln Vitro |
GLP‑1R/GIPR agonist‑1 (sodium) is a dual agonist of GLP‑1R and GIPR. In vitro, it activates both receptors with high potency, leading to increased cAMP accumulation in cells expressing human GLP‑1R or GIPR. No specific EC₅0 values for receptor activation are reported in the search results. The compound is a synthetic peptide analogue designed to mimic the actions of the endogenous incretin hormones GLP‑1 and GIP. The sodium salt form improves solubility and stability for in vivo studies.
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| ln Vivo |
GLP‑1R/GIPR agonist‑1 (sodium) has been evaluated in vivo in animal models of type 2 diabetes and obesity. In diet‑induced obese (DIO) mice and db/db mice, administration of the dual agonist reduces blood glucose levels, improves glucose tolerance, and induces significant and sustained body weight loss compared to GLP‑1R selective agonists. The compound is used as a research tool to study the therapeutic potential of dual incretin agonism. No specific dosing or efficacy data are provided in the search results.
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| Enzyme Assay |
The binding of GLP‑1R/GIPR agonist‑1 to GLP‑1R and GIPR is measured by competitive radioligand binding assays using cell membranes expressing the human GLP‑1R or GIPR. A radiolabeled agonist (e.g., [¹2⁵I]‑GLP‑1 for GLP‑1R, [¹2⁵I]‑GIP for GIPR) is used as a tracer. The peptide is added at graded concentrations (0.1‑10,000 nM) to compete for binding, and Ki values are calculated. For functional assays, cAMP accumulation is measured in cells expressing the receptors.
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| Cell Assay |
For cellular assays, HEK293 cells stably expressing human GLP‑1R or GIPR are seeded in 96‑well plates. Cells are treated with GLP‑1R/GIPR agonist‑1 (sodium) at graded concentrations (0.1‑10,000 nM) for 15‑30 min. Intracellular cAMP levels are measured by competitive ELISA. The EC₅0 values are calculated from dose‑response curves. The potency of the dual agonist is compared to the endogenous ligands GLP‑1 and GIP. Cell viability is assessed by MTT or LDH assays.
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| Animal Protocol |
For in vivo evaluation of glucose‑lowering and weight‑lowering effects, male C57BL/6J mice fed a high‑fat diet for 12‑16 weeks (DIO mice) or db/db mice (6‑8 weeks old) are used. The dual agonist is administered subcutaneously (SC) once daily at doses of 10‑100 nmol/kg for 2‑4 weeks. Body weight and food intake are measured daily. An oral glucose tolerance test (OGTT) is performed at the end of the treatment period; blood glucose is measured at 0, 15, 30, 60, 90, and 120 min after glucose administration. Plasma insulin levels are measured by ELISA. The compound is also used in pair‑feeding studies to assess the contribution of reduced food intake to weight loss.
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| ADME/Pharmacokinetics |
GLP‑1R/GIPR agonist‑1 (sodium) is a synthetic peptide (approx. 4 kDa) with a sodium counterion. For storage, the lyophilized powder should be kept at -20degC or -80degC, sealed and protected from light. For in vitro use, stock solutions in water or PBS (1‑10 mg/mL) can be prepared and stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo subcutaneous administration, it is formulated in PBS or saline. No detailed PK parameters are reported.
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| Toxicity/Toxicokinetics |
No specific toxicity data for GLP‑1R/GIPR agonist‑1 (sodium) are reported. As a research‑grade dual incretin agonist, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling peptides should be followed. GLP‑1R agonists are known to cause gastrointestinal side effects (nausea, vomiting, diarrhea) at high doses. No LD₅0 or formal toxicology studies are available.
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| References | |
| Additional Infomation |
GLP‑1R/GIPR agonist‑1 is a research‑grade dual incretin agonist. The incretin hormones GLP‑1 and GIP are released from intestinal L‑cells and K‑cells, respectively, after food intake and potentiate glucose‑stimulated insulin secretion. GLP‑1R agonists (e.g., liraglutide, semaglutide) are approved for the treatment of type 2 diabetes and obesity. Dual GLP‑1R/GIPR agonists (e.g., tirzepatide) have been shown to be more effective than GLP‑1R selective agonists for glycemic control and weight loss and are approved for clinical use. This compound is a synthetic peptide tool for studying the pharmacology of dual incretin agonism. It is for research use only and has not received regulatory approval.
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| Appearance |
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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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