| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
GLP-1R[1]
The target is the Glucagon-Like Peptide-1 Receptor (GLP-1R), a class B G protein-coupled receptor (GPCR). GLP-1R is a validated therapeutic target for type 2 diabetes and obesity. Activation of GLP-1R in pancreatic beta-cells promotes glucose-dependent insulin secretion, inhibits glucagon release, delays gastric emptying, and promotes satiety. As a PAM, (S)-V-0219 binds to a site distinct from the orthosteric binding site of GLP-1, enhancing the receptor's response to endogenous GLP-1. |
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| ln Vitro |
In HEK cells stably expressing hGLP-1R, (S)-V-0219((S)-9)(0.1 nM) hydrochloride increases calcium flux [1]. High glucose concentrations increase GLP-1-stimulated insulin secretion in the stable human pancreatic cell line EndoC-βH1 when (S)-V-0219(0.1 nM) hydrochloride is added [1].
(S)-V-0219 (0.1 nM) activates calcium flux in HEK cells stably expressing the human GLP-1 receptor (hGLP-1R). As a PAM, it works by potentiating the effect of endogenous GLP-1 rather than directly activating the receptor by itself. The compound is effective at low nanomolar concentrations, and its activity is confirmed by measuring the rise in intracellular calcium in response to sub-maximal GLP-1 stimulation in the presence of the test compound. |
| ln Vivo |
(S)-V-0219 ((S)-9) (0.04-0.2 mg/kg; ip) hydrochloride enhances the way normal male Wistar rats handle glucose after receiving a 2 g/kg injection [1]. In Zucker rats with diabetes who are obese, (S)-V-0219 (0. 4 mg/kg; ig) hydrochloride has oral activity [1]. In male Wistar rats that have fasted for 12 hours, (S)-V-0219 (0.1–5 μg/kg in 5 μL; icv) hydrochloride decreases food intake [1].
In animal models, V-0219 (the racemate) has demonstrated the ability to improve high glucose levels in mice and suppress feeding behavior in fasted mice. The active S-enantiomer is responsible for these in vivo effects. By allosterically potentiating GLP-1 signaling, the compound helps regulate blood glucose homeostasis and reduces food intake, making it a candidate for the oral treatment of "Diabesity" (diabetes and obesity). |
| Enzyme Assay |
The activity of V-0219 was identified and characterized using cell-based functional assays rather than isolated enzyme binding. The primary assay measures the potentiation of GLP-1-induced calcium mobilization. HEK-293 cells expressing hGLP-1R were loaded with Fluo-4 (a calcium indicator). The cells were stimulated with a submaximal concentration of GLP-1, and the fluorescence signal was recorded to determine the EC50 values for the test compound.
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| Cell Assay |
The same cell-based calcium flux protocol is used to assess cellular potency. Specifically, HEK cells stably expressing hGLP-1R are seeded into 384-well plates. After loading with calcium dye, the plate is placed in a FLIPR (Fluorometric Imaging Plate Reader) instrument. (S)-V-0219 is added at varying concentrations, and the change in fluorescence is measured to confirm receptor activation. The EC50 for activation of GLP-1R by V-0219 was reported as 10 nM.
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| Animal Protocol |
The in vivo efficacy of V-0219 (or its racemate) is evaluated in mouse models of obesity and diabetes (e.g., high-fat diet-induced obesity (DIO) mice or db/db mice). Animals are administered the compound via oral gavage (e.g., 10-30 mg/kg). For efficacy, an oral glucose tolerance test (OGTT) is performed: blood glucose levels are measured before and after glucose challenge. For feeding behavior, food intake is monitored over 4-24 hours post-dosing in fasted mice.
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| ADME/Pharmacokinetics |
(S)-V-0219 is an orally bioavailable small molecule (MW 446.89). It is highly soluble in DMSO (100 mg/mL). For in vivo studies, it can be formulated in a vehicle such as 10% DMSO in saline or a mixture of DMSO/PEG300/Tween-80/saline to achieve a clear solution for oral gavage. The half-life and specific clearance values are not publicly detailed but are consistent with an orally active, once-daily dosing profile.
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| Toxicity/Toxicokinetics |
As a research compound, toxicity data is limited. GLP-1R agonists as a class are generally well-tolerated, with the most common side effects being gastrointestinal in nature (nausea, vomiting, diarrhea) when dosed orally. Because (S)-V-0219 is a PAM, it may have an improved side effect profile compared to orthosteric agonists, as its activity is dependent on the presence of endogenous GLP-1, potentially reducing the risk of hypoglycemia.
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| References | |
| Additional Infomation |
(S)-V-0219 hydrochloride is a research-grade chemical tool. The discovery of V-0219 as a small-molecule GLP-1R PAM for oral treatment of type 2 diabetes and obesity (termed "Diabesity") was published in the Journal of Medicinal Chemistry (Decara JM et al., 2022). This product is not a clinical drug and has not received FDA approval. It is strictly for research applications, targeting the GLP-1 receptor for metabolic disease studies.
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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;(R)-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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