| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
GLP-1R[1]
GLP-1 receptor (GLP-1R). V-0219 acts as a positive allosteric modulator (PAM), binding to a site distinct from the orthosteric GLP-1 binding pocket and potentiating the receptor‘s response to the endogenous agonist. |
|---|---|
| ln Vitro |
In HEK293 cells stably expressing human GLP-1R, (R)-V-0219 hydrochloride at 0.1 nM causes GLP-1-stimulated receptor activation with an EC50 of 10 nM. It stimulates calcium flux, confirming its PAM activity in potentiating GLP-1R signaling in a cell-based functional assay.
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| ln Vivo |
V-0219 hydrochloride demonstrates oral bioavailability and is utilized in studies of obesity-related diabetes. As an orally active GLP-1R PAM, it enhances endogenous GLP-1 signaling, which contributes to improved glycemic control and potential weight loss in animal models of metabolic disease.
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| Enzyme Assay |
A cell-free binding assay for GLP-1R PAMs is performed using membrane preparations. Membranes expressing human GLP-1R are incubated with a fixed concentration of [125I]GLP-1 and various concentrations of V-0219 hydrochloride in the presence of a low concentration of GLP-1. After incubation, bound and free ligands are separated by filtration, and radioactivity is counted to assess allosteric modulation.
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| Cell Assay |
A standard cellular assay involves seeding HEK293 cells stably expressing human GLP-1R in 96-well plates. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4). After incubation, cells are treated with a submaximal concentration of GLP-1 plus varying concentrations of V-0219, and fluorescence intensity is measured to quantify calcium flux and determine PAM potentiation.
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| Animal Protocol |
In vivo efficacy is evaluated in diet-induced obese (DIO) mouse models. V-0219 hydrochloride is administered orally. Endpoints include measurements of blood glucose levels, oral glucose tolerance, food intake, and body weight. Blood samples are collected at various time points to assess PK/PD relationships.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of V-0219 are characteristic of an orally available small molecule. Following oral administration, it reaches peak plasma concentrations (Cmax) within a few hours and has a half-life suitable for once or twice daily dosing. Bioavailability and metabolic stability contribute to its efficacy in vivo.
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| Toxicity/Toxicokinetics |
Not reported. No standardized toxicology data is currently available for V-0219 hydrochloride as it is a research compound. Positive allosteric modulators of GPCRs often exhibit improved safety profiles compared to orthosteric agonists due to their modulatory, rather than activating, mechanism.
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| References | |
| Additional Infomation |
Unlike traditional GLP-1 receptor agonists (e.g., Exenatide, Liraglutide) which are peptide-based and require injection, V-0219 is an orally available small molecule positive allosteric modulator. Its mechanism of enhancing, rather than directly activating, GLP-1R signaling may offer improved tolerability and reduced risk of side effects such as nausea and vomiting, while also potentially providing synergistic benefits when combined with endogenous GLP-1 secretion from DPP-4 inhibitors.
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| Molecular Formula |
C20H26CLF3N4O2
|
|---|---|
| Molecular Weight |
446.894254207611
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| Exact Mass |
446.169
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| CAS # |
2922283-73-4
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| Related CAS # |
V-0219;878453-71-5;(R)-V-0219 hydrochloride;(S)-V-0219 hydrochloride;(R)-V-0219;(S)-V-0219
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| PubChem CID |
166604052
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| Appearance |
White to off-white solid powder
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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 |
5
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| Heavy Atom Count |
30
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| Complexity |
510
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(CN(C1)CC2=NC(=NO2)C3=CC=C(C=C3)C(F)(F)F)CN4CCOCC4.Cl
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| InChi Key |
PTRIYHLSBQMDQM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25F3N4O2.ClH/c21-20(22,23)17-5-3-16(4-6-17)19-24-18(29-25-19)14-27-7-1-2-15(13-27)12-26-8-10-28-11-9-26;/h3-6,15H,1-2,7-14H2;1H
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| Chemical Name |
4-[[1-[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-3-yl]methyl]morpholine;hydrochloride
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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) |
DMSO: 100 mg/mL (223.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.59 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 25.0 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: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2377 mL | 11.1884 mL | 22.3769 mL | |
| 5 mM | 0.4475 mL | 2.2377 mL | 4.4754 mL | |
| 10 mM | 0.2238 mL | 1.1188 mL | 2.2377 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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