| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Other Sizes |
| Targets |
Glucagon-like peptide-1 receptor (GLP-1R). V-0219 acts as a positive allosteric modulator (PAM) of GLP-1R, enhancing the receptor's response to endogenous GLP-1 without directly activating the receptor on its own. This mechanism amplifies glucose-dependent insulin secretion, promotes satiety, and reduces food intake. Binding of V-0219 to an allosteric site on GLP-1R increases the affinity and/or efficacy of orthosteric GLP-1 binding.
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| ln Vitro |
In cell-free biochemical assays, V-0219 enhances GLP-1-induced cAMP production in membranes expressing human GLP-1R. Typically, membranes are incubated with varying concentrations of GLP-1 (0-100 nM) with or without a fixed concentration of V-0219 (e.g., 1-10 uM). cAMP levels are measured using HTRF (homogeneous time-resolved fluorescence) or ELISA-based methods. The PAM effect is demonstrated by a leftward shift in the GLP-1 dose-response curve. The compound has no significant agonist activity (maximal efficacy <10% of GLP-1) in the absence of orthosteric ligand.
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| ln Vivo |
V-0219 potentiates insulin secretion in INS-1 beta-cells with an EC50 of 0.25 nM. The best response is observed at 0.1 nM when a fixed concentration of 0.2 nM GLP-1 is added to the dose-response curve, with maximal response plateau at 0.1 nM and an EC50 of 0.008 nM. In HEK293 cells stably expressing hGLP-1R, V-0219 activates calcium flux. The Emax in cAMP assays is 60%, indicating partial PAM activity. V-0219 shows no significant off-target activities against related GPCRs or other receptor classes.
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| Enzyme Assay |
To assess PAM activity on GLP-1R, cell-free membrane-based cAMP assays are used. Membranes prepared from HEK293 or CHO cells expressing recombinant human GLP-1R are incubated with V-0219 (0.1 nM-10 uM) in the presence of a submaximal concentration of GLP-1 (e.g., EC20-EC30, typically 0.2-1 nM). cAMP production is measured using HTRF or AlphaScreen technology. The EC50 for PAM activity is defined as the concentration of V-0219 producing 50% of the maximal potentiation of GLP-1-induced cAMP accumulation. Fold-potentiation and Emax values are calculated relative to GLP-1 alone.
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| Cell Assay |
Insulin secretion assays are performed using INS-1 rat pancreatic beta-cells or primary mouse islets. Cells are cultured in RPMI 1640 medium with 10% FBS and beta-mercaptoethanol. For secretion assays, cells are pre-incubated in Krebs-Ringer bicarbonate buffer (KRB) with low glucose (2.8 mM) for 1 hour. Then, cells are incubated with V-0219 (0.001-10 uM) and/or GLP-1 (0.01-100 nM) in KRB containing stimulatory glucose (11.1-16.7 mM) for 1 hour. Supernatants are collected, and insulin concentration is measured by ELISA. EC50 values for insulin secretion potentiation are calculated. Calcium flux in hGLP-1R-HEK293 cells is measured using Fluo-4 AM or similar calcium-sensitive dyes by fluorescence imaging.
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| Animal Protocol |
In normal and diabetic rodents, V-0219 shows remarkable in vivo activity, reducing food intake and improving glucose handling. The compound demonstrates oral efficacy in rodent models of food intake and glucose regulation. (S)-V-0219, the active enantiomer, improves hyperglycemia in mice and inhibits feeding behavior in fasted mice. Typical study designs include acute oral glucose tolerance tests (OGTT), chronic dosing studies (2-4 weeks), and food intake measurements. For OGTT, mice are fasted overnight, orally dosed with V-0219 (1-30 mg/kg), then challenged with glucose (2 g/kg) 30 minutes later, with blood glucose measured over 120 minutes.
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| ADME/Pharmacokinetics |
V-0219 is orally bioavailable, supporting oral administration as the intended route. The compound is rapidly absorbed following oral dosing, with Tmax typically achieved within 0.5-2 hours in rodents. The half-life in preclinical species is approximately 2-6 hours, supporting once- or twice-daily dosing. The compound shows good plasma exposure and distributes to target tissues. The (S) enantiomer is the active species. Pharmacokinetic studies in animal models demonstrate dose-proportional exposure and low-to-moderate plasma protein binding. V-0219 is metabolized primarily by CYP450 enzymes, likely CYP3A4. Excretion is primarily via feces and urine.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies indicate that V-0219 has an acceptable safety margin for the intended indication. The compound is generally well-tolerated at therapeutic doses in animal models without significant adverse effects. Common adverse events associated with GLP-1R agonists, such as nausea and gastrointestinal distress, are expected to be reduced with PAMs due to the glucose-dependent mechanism and lower risk of receptor overstimulation. For research use, standard laboratory safety practices should be followed. Detailed acute and repeat-dose toxicity data have not been publicly disclosed.
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| References | |
| Additional Infomation |
V-0219 was discovered and characterized in research published in the Journal of Medicinal Chemistry (2022). The compound is also known as Compound 9 in the primary literature. The (S) enantiomer is the biologically active species. V-0219 represents a novel approach to treating "diabesity" (obesity-associated diabetes) through oral GLP-1R PAM therapy, potentially offering advantages over injectable GLP-1R agonists. The compound is not approved for clinical use and is intended for research applications only. The molecular formula is C20H25F3N4O2.
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| Molecular Formula |
C20H25F3N4O2
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|---|---|
| Molecular Weight |
410.433315038681
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| Exact Mass |
410.193
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| CAS # |
878453-71-5
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| Related CAS # |
V-0219 hydrochloride;2922283-73-4;(R)-V-0219 hydrochloride;(S)-V-0219 hydrochloride;(R)-V-0219;(S)-V-0219
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| PubChem CID |
6486002
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| Appearance |
Light yellow to yellow ointment
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| LogP |
3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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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
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| InChi Key |
VFQGZIAZHIRPPQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25F3N4O2/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
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| Chemical Name |
4-((1-((3-(4-(trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)piperidin-3-yl)methyl)morpholine
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| Synonyms |
V0219 V-0219 V 0219
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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 (~243.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.07 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 20.8 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: ≥ 2.08 mg/mL (5.07 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 20.8 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: ≥ 2.08 mg/mL (5.07 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 | 2.4365 mL | 12.1823 mL | 24.3647 mL | |
| 5 mM | 0.4873 mL | 2.4365 mL | 4.8729 mL | |
| 10 mM | 0.2436 mL | 1.2182 mL | 2.4365 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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