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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
GLP-1 receptor (GLP-1R), a class B G protein-coupled receptor (GPCR) primarily expressed in pancreatic beta-cells, the central nervous system, and gastrointestinal tract. GLP-1R activation stimulates insulin secretion in response to elevated blood glucose, inhibits glucagon release, delays gastric emptying, and promotes satiety. As a positive allosteric modulator (PAM), (R)-V-0219 binds to a site distinct from the orthosteric GLP-1 binding site, enhancing receptor activation without directly activating the receptor itself.
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| ln Vitro |
(R)-V-0219 (0.1 nM) hydrochloride causes GLP-1-stimulated receptor activation with an EC50 value of 10 nM and stimulates calcium flux in HEK cells that are stable hGLP-1R expression [1].
In vitro, (R)-V-0219 (0.1 nM) is capable of activating calcium fluxes in HEK cells stably expressing the human GLP-1 receptor. It induces receptor activation stimulated by GLP-1 with an EC50 value of 10 nM. As a PAM, it potentiates the effect of endogenous GLP-1 rather than directly activating the receptor on its own. This selectivity profile may reduce the risk of desensitization and off-target effects compared to orthosteric agonists. |
| ln Vivo |
As a research compound, detailed in vivo efficacy data for (R)-V-0219 specifically is limited. The parent compound V-0219 was designed for oral treatment of diabesity (obesity-related diabetes). In rodent models of type 2 diabetes, V-0219 is expected to improve glucose tolerance and reduce body weight through its GLP-1R PAM activity. Being a PAM, it potentiates endogenous GLP-1, potentially reducing the hypoglycemia risk associated with GLP-1 orthosteric agonists.
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| Enzyme Assay |
A cell-based functional assay is used to assess GLP-1R PAM activity. HEK293 cells stably transfected with human GLP-1R are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 AM). Cells are pre-incubated with varying concentrations of (R)-V-0219 hydrochloride (0.01-1000 nM), then stimulated with a submaximal concentration of GLP-1 (e.g., 1 nM). Fluorescence intensity (λ_ex 488 nm, λ_em 525 nm) is measured to calculate EC50 values.
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| Cell Assay |
A PAM activity assay is performed using HEK293 cells stably expressing human GLP-1R and a cAMP response element (CRE)-luciferase reporter. Cells are seeded in 96-well plates and co-treated with varying concentrations of (R)-V-0219 hydrochloride (0.01-1000 nM) and a submaximal concentration of GLP-1 (e.g., 0.1 nM). After 4-6 hours, luciferase activity is measured. The EC50 for potentiation of GLP-1 signaling is calculated. As a control, cells treated with compound alone (without GLP-1) should show no activation.
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| Animal Protocol |
For the parent compound V-0219, in vivo efficacy is evaluated in rodent models of type 2 diabetes and obesity. Male C57BL/6J mice fed a high-fat diet (HFD) or db/db mice are orally administered V-0219 (doses 1-30 mg/kg) once daily for 2-4 weeks. Oral glucose tolerance tests (OGTT) are performed to measure glucose lowering. Body weight, food intake, and plasma insulin levels are monitored. Pancreatic sections are analyzed for beta-cell preservation by insulin immunohistochemistry.
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| ADME/Pharmacokinetics |
(R)-V-0219 hydrochloride has good solubility in DMSO (100 mg/mL) and is cell-permeable, making it suitable for in vitro assays. For in vivo formulation, it is typically dissolved in PEG400/saline or DMSO/PEG400/water mixtures. As a small molecule PAM (MW 446.89), it has favorable drug-like properties and is expected to have moderate to high oral bioavailability based on parent compound V-0219 being described as "orally active." Detailed PK parameters such as half-life, clearance, and volume of distribution are not publicly available for this research compound.
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| Toxicity/Toxicokinetics |
Toxicology data specific to (R)-V-0219 hydrochloride is not publicly available. GLP-1R modulators as a class have known adverse effects including gastrointestinal disturbances (nausea, vomiting, diarrhea), which are typically mild to moderate and often attenuate with continued dosing. As a PAM rather than an orthosteric agonist, (R)-V-0219 may have an improved tolerability profile due to activity-dependent (glucose-dependent) insulin secretion and reduced risk of desensitization or receptor downregulation.
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| References | |
| Additional Infomation |
V-0219 (as the racemate or parent compound) was discovered as a novel small-molecule positive allosteric modulator (PAM) of GLP-1R for the oral treatment of type 2 diabetes and obesity ("Diabesity"). The discovery and characterization of V-0219 was published in the Journal of Medicinal Chemistry in April 2022 by Decara JM and colleagues. As a research compound, V-0219 and its enantiomers are not FDA-approved and have not yet progressed to clinical trials based on publicly available information. These products are intended for preclinical research use only.
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| Molecular Formula |
C20H26CLF3N4O2
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|---|---|
| Molecular Weight |
446.89
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| Related CAS # |
V-0219;878453-71-5;V-0219 hydrochloride;2922283-73-4;(S)-V-0219 hydrochloride;(R)-V-0219;(S)-V-0219
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| Appearance |
White to off-white solid powder
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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) |
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 | 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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