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| 10mg |
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| Targets |
GLP-1 receptor (GLP-1R). GLP-1 receptor agonist 10 is a selective small-molecule agonist of the glucagon-like peptide-1 receptor, a class B G protein-coupled receptor. Activation of GLP-1R by this compound stimulates downstream signaling pathways, primarily via Gs protein coupling leading to adenylate cyclase activation and increased intracellular cAMP levels. Elevated cAMP activates PKA and Epac2, which potentiate glucose-stimulated insulin secretion from pancreatic beta-cells. Unlike peptide GLP-1R agonists, small-molecule agonists such as this compound may achieve oral bioavailability and distinct signaling bias profiles.
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| ln Vitro |
No specific in vitro data are available for GLP-1 receptor agonist 10. As a representative small-molecule GLP-1R agonist, it would be expected to activate GLP-1R in cell-based assays such as cAMP accumulation assays. HEK293 cells stably expressing human GLP-1R are typically treated with varying compound concentrations (0.1 pM to 10 uM) for 30 minutes at 37degC. Intracellular cAMP levels are measured using HTRF or chemiluminescence detection kits. EC50 values in the low nanomolar to sub-nanomolar range are anticipated, based on the structure-activity relationship of related small-molecule GLP-1R agonists.
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| ln Vivo |
In vivo, GLP-1 receptor agonist 10 inhibits food intake and reduces glucose excursions in mice. Standard preclinical evaluation: Male C57BL/6J mice are orally administered with GLP-1 receptor agonist 10 (0.1-10 mg/kg) or vehicle 30 minutes prior to an oral glucose tolerance test (OGTT). Blood glucose levels are measured at 0, 15, 30, 60, 90, and 120 minutes post-glucose challenge. For food intake studies, mice are fasted overnight and then administered compound or vehicle just prior to the start of the dark cycle, and cumulative food consumption is measured at 1, 2, 4, 8, and 24 hours. Acute and chronic dosing regimens can be employed to assess glycemic control and body weight effects.
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| Enzyme Assay |
For direct binding assays, the human GLP-1 receptor (GLP-1R) can be immobilized on a sensor chip for surface plasmon resonance (SPR). GLP-1 receptor agonist 10 at concentrations ranging from 1 nM to 10 uM is flowed over the immobilized receptor in running buffer (e.g., HBS-EP+). Binding affinity (KD) is determined by fitting the association and dissociation phases to a 1:1 Langmuir binding model. Alternatively, competitive radioligand binding assays may be performed: membranes from CHO-K1 cells expressing human GLP-1R are incubated with 0.1 nM 125I-GLP-1(7-36) amide and varying concentrations of unlabeled test compound in 96-well plates for 2 hours at 25degC. Bound radioligand is separated by filtration, and radioactivity is quantified to calculate IC50 and Ki values.
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| Cell Assay |
No specific cellular assay protocols are available for GLP-1 receptor agonist 10. A standard cAMP accumulation assay using HEK293 cells stably expressing human GLP-1R (GLP-1R-HEK293 cells) can be used. Cells are seeded in 96-well plates at 2-5 × 10^4 cells per well and cultured overnight. After removal of culture medium, cells are incubated with 0.5 mM IBMX (phosphodiesterase inhibitor) in assay buffer for 20 minutes at 37degC. Cells are then treated with varying concentrations of compound (0.1 pM to 10 microM) for 30 minutes at 37degC. Cells are lysed, and cAMP levels are measured using a homogeneous time-resolved fluorescence (HTRF) or chemiluminescence-based detection kit. EC50 is calculated using a four-parameter logistic curve. The assay may be performed in both agonist and antagonist modes.
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| Animal Protocol |
For in vivo pharmacodynamic assessment, female or male C57BL/6 mice (8-12 weeks old) are used. Compound is formulated in appropriate vehicle (e.g., 10% DMSO, 40% PEG400, 5% Tween 80 in water or 0.5% methylcellulose) and administered orally by gavage at a dosing volume of 10 mL/kg at doses of 0.3, 1, 3, or 10 mg/kg. For IPGTT, mice are fasted for 5-6 hours, compound is administered 30 minutes prior to glucose challenge (2 g/kg glucose solution, i.p.). Blood glucose is measured by glucometer at -30, 0, 15, 30, 60, 90, 120, and 180 minutes post-glucose. Blood samples (20 uL) from tail vein are collected into heparinized capillary tubes, and plasma is separated by centrifugation for insulin ELISA measurement. For food intake, mice are fasted overnight (16-18 hours), weighed, and administered compound just prior to dark cycle onset. Pre-weighed food pellets are placed in cages, and remaining food is weighed at 1, 2, 4, 6, 8, 12, and 24 hours post-dosing.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are available for GLP-1 receptor agonist 10. As a small-molecule compound with oral activity, it is anticipated to have moderate-to-good oral bioavailability. The terminal elimination half-life in mice is expected to be in the range of 2-6 hours, supporting once- or twice-daily dosing in preclinical studies. The compound is likely to have moderate plasma protein binding and to undergo hepatic metabolism via cytochrome P450 enzymes. The small-molecule scaffold is designed to overcome the peptide-like pharmacokinetic limitations of native GLP-1, potentially enabling oral administration. Detailed PK parameters (AUC, Cmax, Tmax, CL) are typically determined from plasma concentration-time profiles after oral and intravenous administration.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available for GLP-1 receptor agonist 10. Based on its mechanism as a GLP-1R agonist, potential adverse effects may include gastrointestinal disturbances (nausea, vomiting, diarrhea) consistent with the known effects of GLP-1R activation. No genotoxicity, organ toxicity, or carcinogenicity has been reported for this compound. In animal studies, high doses may cause decreased food intake and body weight loss as pharmacodynamic effects rather than toxic responses. The compound should be handled as a potential hazardous chemical with appropriate laboratory safety practices. Long-term chronic toxicity studies have not been reported for this investigational compound.
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| References | |
| Additional Infomation |
GLP-1 receptor agonist 10 (compound 42) is a small-molecule GLP-1 receptor agonist developed as a research tool for studying type 2 diabetes and obesity. Unlike peptide-based GLP-1R agonists (e.g., liraglutide, semaglutide) which require injection, small-molecule GLP-1R agonists have the potential for oral administration. As of 2026, no small-molecule GLP-1R agonist has received FDA approval, although several are in clinical development (e.g., Eli Lilly's LY3502970/orforglipron). GLP-1 receptor agonist 10 is for research use only. It represents a chemical scaffold distinct from the native peptide hormone, offering a tool to investigate GLP-1R signaling and therapeutic potential in T2DM and obesity.
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| Molecular Formula |
C30H28F4N6O5
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| Molecular Weight |
628.57
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| Exact Mass |
628.206
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| CAS # |
3015555-46-8
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| PubChem CID |
166524256
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| Appearance |
Off-white to yellow solid powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
45
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| Complexity |
1040
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=C(C=CC(=C1)C(F)(F)F)COC2=CC=CC(=N2)N3CCN(N=C3)CC4=NC5=C(N4C[C@@H]6CCO6)C=C(C=C5F)C(=O)O
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| InChi Key |
ARRGUNBLOBTMBV-NRFANRHFSA-N
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| InChi Code |
InChI=1S/C30H28F4N6O5/c1-43-24-13-20(30(32,33)34)6-5-18(24)16-45-27-4-2-3-25(36-27)38-8-9-39(35-17-38)15-26-37-28-22(31)11-19(29(41)42)12-23(28)40(26)14-21-7-10-44-21/h2-6,11-13,17,21H,7-10,14-16H2,1H3,(H,41,42)/t21-/m0/s1
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| Chemical Name |
7-fluoro-2-[[4-[6-[[2-methoxy-4-(trifluoromethyl)phenyl]methoxy]-2-pyridinyl]-5,6-dihydro-1,2,4-triazin-1-yl]methyl]-3-[[(2S)-oxetan-2-yl]methyl]benzimidazole-5-carboxylic acid
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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 |
| 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 (~198.86 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 | 1.5909 mL | 7.9546 mL | 15.9091 mL | |
| 5 mM | 0.3182 mL | 1.5909 mL | 3.1818 mL | |
| 10 mM | 0.1591 mL | 0.7955 mL | 1.5909 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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