| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Glucagon receptor (GR) (Ki = 0.8 nM; cAMP inhibition IC₅₀ = 2.3 nM) [1]
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|---|---|
| ln Vitro |
Glucagon receptor antagonists-2 is a 4-aryl-pyridine-derived glucagon receptor antagonist with high binding affinity and functional inhibitory activity. [1]
In the glucagon receptor binding assay, Glucagon receptor antagonists-2 exhibited a Ki value of 0.8 nM, indicating strong binding to the glucagon receptor. [1] In the functional cAMP accumulation assay, Glucagon receptor antagonists-2 dose-dependently inhibited glucagon-induced cAMP production in cells expressing human glucagon receptor, with an IC₅₀ value of 2.3 nM. [1] The compound maintained high potency after optimization of substituent patterns on the 4-aryl-pyridine scaffold, outperforming earlier analogs in both binding affinity and functional inhibition. [1] |
| Enzyme Assay |
Glucagon receptor binding assay: Membrane preparations containing human glucagon receptor were incubated with a fixed concentration of radiolabeled glucagon and serial dilutions of Glucagon receptor antagonists-2. After incubation, the bound and free radioligands were separated by filtration, and the radioactivity of the bound fraction was measured. The Ki value was calculated based on the displacement of radiolabeled glucagon by the compound. [1]
cAMP accumulation inhibitory assay: Cells stably expressing human glucagon receptor were seeded and pre-incubated with Glucagon receptor antagonists-2 at various concentrations. Glucagon was then added to stimulate cAMP production. After a specified incubation period, the cells were lysed, and the intracellular cAMP level was quantified using a competitive binding assay. The IC₅₀ value was determined by plotting the percentage of cAMP inhibition against the compound concentration. [1] |
| References | |
| Additional Infomation |
Glucagon receptor antagonists-2 were developed by integrating an optimized substituent pattern onto a 4-arylpyridine core backbone, a strategy designed to enhance the binding affinity and functional potency of the glucagon receptor. [1] Glucagon receptor antagonists are potential drugs for the treatment of type 2 diabetes because they can block glucagon-mediated increases in hepatic glucose output, thereby lowering blood glucose levels. [1] The 4-arylpyridine backbone was chosen as the target for optimization of glucagon receptor antagonists-2 because of its structural properties that are favorable for receptor binding, including suitable steric hindrance and the potential to form hydrogen bonds with the active site of the glucagon receptor. [1]
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| Molecular Formula |
C22H30FNO2
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|---|---|
| Molecular Weight |
359.48
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| Exact Mass |
361.24
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| CAS # |
202917-18-8
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| Related CAS # |
Glucagon receptor antagonists-3; 202917-17-7
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| PubChem CID |
77147236
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| Appearance |
Solid powder
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| Density |
1.085
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| Boiling Point |
469.6ºC at 760 mmHg
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| Flash Point |
237.8ºC
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| LogP |
5.548
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
552
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OINVVPOIGFSNHM-VLIAUNLRSA-N
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| InChi Code |
InChI=1S/C22H32FNO2/c1-7-8-17-20(16-10-9-15(23)11-18(16)26)19(14(6)25)22(13(4)5)24-21(17)12(2)3/h9-14,20,24-26H,7-8H2,1-6H3/t14-,20+/m1/s1
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| Chemical Name |
5-fluoro-2-[(4S)-3-[(1R)-1-hydroxyethyl]-2,6-di(propan-2-yl)-5-propyl-1,4-dihydropyridin-4-yl]phenol
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| Synonyms |
Glucagon receptor antagonists-2
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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: ~16.7 mg/mL (~46.4 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (4.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (4.65 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 16.7 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 | 2.7818 mL | 13.9090 mL | 27.8180 mL | |
| 5 mM | 0.5564 mL | 2.7818 mL | 5.5636 mL | |
| 10 mM | 0.2782 mL | 1.3909 mL | 2.7818 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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