| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Targets |
GLP-1R Antagonist 1 specifically targets the glucagon-like peptide 1 receptor (GLP-1R), a class B G protein-coupled receptor involved in glucose homeostasis and insulin secretion. As a non-competitive antagonist, it binds to a site distinct from the orthosteric binding site of GLP-1, blocking receptor signaling without competing with the endogenous ligand. The compound’s CNS penetrant property allows it to access central GLP-1R populations. By blocking GLP-1R, it inhibits GLP-1-induced insulin secretion and leads to elevated blood glucose levels.
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| ln Vitro |
In vitro, GLP-1R Antagonist 1 demonstrates potent antagonism of GLP-1R with an IC50 of 650 nM. The compound effectively blocks GLP-1-induced signaling in cell-based assays. Its non-competitive mechanism of action is confirmed through receptor binding and functional studies. The compound shows CNS penetrant properties in vitro. It is typically evaluated in cell lines expressing recombinant GLP-1R using cAMP accumulation assays or calcium flux measurements to assess receptor activity. The compound’s potency and selectivity are determined through dose-response experiments with appropriate controls.
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| ln Vivo |
In vivo, GLP-1R Antagonist 1 (10 mg/kg, oral administration) increases blood glucose levels and decreases blood insulin levels in male Sprague-Dawley rats. This effect is consistent with GLP-1R blockade, which reduces glucose-stimulated insulin secretion. The compound’s oral activity and CNS penetration have been demonstrated in preclinical studies. These in vivo effects confirm the compound’s utility as a pharmacological tool for studying GLP-1R function and glucose metabolism. The compound is typically administered in formulations such as 10% DMSO + 90% corn oil.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for GLP-1R Antagonist 1 involve radioligand binding displacement studies using membranes from cells expressing recombinant human GLP-1R. The compound’s IC50 of 650 nM is determined through competitive binding assays with labeled GLP-1 or GLP-1 analogs. Functional antagonism is assessed by measuring the compound’s ability to inhibit GLP-1-stimulated cAMP production in cell-based assays. Non-competitive binding is confirmed through Schild analysis or kinetic binding studies. Assays are performed in appropriate buffer systems with positive controls such as known GLP-1R antagonists.
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| Cell Assay |
In vitro cell-based assays for GLP-1R Antagonist 1 are conducted in cell lines expressing recombinant GLP-1R, such as HEK293 or CHO cells. Cells are cultured in appropriate media at 37°C with 5% CO2. For functional assays, cells are treated with the compound at varying concentrations (typically 0.1-100 μM) prior to stimulation with GLP-1 or GLP-1 analogs. cAMP accumulation is measured using ELISA or HTRF-based detection methods. IC50 values are calculated from dose-response curves. Cell viability is assessed to ensure compound concentrations are not cytotoxic. Experiments are performed in triplicate with appropriate vehicle controls.
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| Animal Protocol |
In vivo animal studies for GLP-1R Antagonist 1 are conducted in male Sprague-Dawley rats. The compound is administered orally at doses such as 10 mg/kg. Blood samples are collected at various time points to measure glucose and insulin levels. Oral glucose tolerance tests may be performed to assess the compound’s effect on glucose homeostasis. The compound is formulated in vehicles such as 10% DMSO + 90% corn oil for oral administration. Animals are monitored for clinical signs, and pharmacokinetic parameters may be determined from plasma samples. Studies are conducted in accordance with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
GLP-1R Antagonist 1 is orally active and CNS penetrant, with favorable drug-like properties. Its molecular weight is 440.73 g/mol, and it has a molecular formula of C16H11ClF6N4O2. The compound is soluble in DMSO (90 mg/mL). For in vivo studies, it can be formulated in 10% DMSO + 90% corn oil. The compound shows stability under recommended storage conditions (powder at -20°C for 3 years, in solvent at -80°C for 1 year). Pharmacokinetic parameters such as oral bioavailability, half-life, and tissue distribution would be determined in species-specific studies.
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| Toxicity/Toxicokinetics |
Toxicological data for GLP-1R Antagonist 1 are limited as the compound is a research tool. In preclinical studies, the compound has shown acceptable tolerability at the doses used for pharmacological evaluation. Standard safety precautions should be followed when handling. The compound is intended for research use only. Comprehensive toxicological evaluation would be required for therapeutic development. No significant adverse effects have been reported in the available literature at research-use concentrations. The compound should be handled with appropriate personal protective equipment in a laboratory setting.
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| Additional Infomation |
GLP-1R Antagonist 1 (compound 5d) is an orally active, CNS penetrant, non-competitive antagonist of GLP-1R with an IC50 of 650 nM. It serves as a valuable pharmacological tool for studying GLP-1R-mediated signaling pathways and glucose homeostasis. By blocking GLP-1R, the compound elevates blood glucose and reduces insulin secretion, providing insights into GLP-1 physiology. The compound has potential applications in diabetes research, obesity studies, and neuroscience. All applications are limited to non-human research use. The compound is not approved for human therapeutic use.
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| Molecular Formula |
C16H11CLF6N4O2
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|---|---|
| Molecular Weight |
440.727563142776
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| Exact Mass |
440.047
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| CAS # |
488097-06-9
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| PubChem CID |
1941609
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
29
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| Complexity |
784
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MFEIZMHODFOWAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11ClF6N4O2/c1-26-11-9(12(28)27(2)13(26)29)14(15(18,19)20,16(21,22)23)25-10(24-11)7-3-5-8(17)6-4-7/h3-6H,1-2H3,(H,24,25)
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| Chemical Name |
7-(4-chlorophenyl)-1,3-dimethyl-5,5-bis(trifluoromethyl)-8H-pyrimido[4,5-d]pyrimidine-2,4-dione
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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 : ~100 mg/mL (~226.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.67 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2690 mL | 11.3448 mL | 22.6896 mL | |
| 5 mM | 0.4538 mL | 2.2690 mL | 4.5379 mL | |
| 10 mM | 0.2269 mL | 1.1345 mL | 2.2690 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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