| Size | Price | Stock | Qty |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Other Sizes |
| Targets |
mAChR M5 ( IC50 = 4.1 μM ); mAChR M1 ( IC50 = 6.1 μM ); mAChR M3 ( IC50 = 6.4 μM )
VU0119498 targets the M1, M3, and M5 subtypes of muscarinic acetylcholine receptors (mAChRs), which are G protein-coupled receptors that signal through the Gq pathway. As a positive allosteric modulator (PAM), VU0119498 binds to an allosteric site on the receptor, distinct from the orthosteric (acetylcholine) binding site. This binding enhances the receptor's response to acetylcholine, potentiating its signaling without directly activating the receptor itself. |
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| ln Vitro |
VU0119498 (0.01-30 μM; 150 s) amplifies Ach responses in M1, M3, and M5-expressing CHO cells, with EC50s of 6.04, 6.38, and 4.08 µM, respectively[1].
VU0119498 (3–20 μM) enhances ACh-mediated increases in insulin secretion and intracellular calcium levels in MIN6-K8 cells[3]. VU0119498 (20 μM; 90 min) improves ACh-induced insulin release in mouse and human pancreatic islets[3]. In vitro, VU0119498 (0.01-30 µM; 150 seconds) amplifies acetylcholine (ACh) responses in M1, M3, and M5-expressing CHO cells, with EC50s of 6.04, 6.38, and 4.08 µM, respectively. VU0119498 (3–20 µM) enhances ACh-mediated increases in insulin secretion and intracellular calcium levels in MIN6-K8 cells. VU0119498 (20 µM; 90 minutes) improves ACh-induced insulin release in mouse and human pancreatic islets. |
| ln Vivo |
VU0119498 (0.1-2 mg/kg; a single i.p.) enhances insulin secretion and glucose tolerance in mice in a β-cell M3R-dependent manner[3].
VU0119498 (0.5 mg/kg; a single intraperitoneal; I.P.) enhances both glucose tolerance and insulin secretion in obese, glucose-intolerant mice[3]. In vivo, VU0119498 (0.1-2 mg/kg; a single i.p.) enhances insulin secretion and glucose tolerance in mice in a β-cell M3R-dependent manner. VU0119498 (0.5 mg/kg; a single i.p.) enhances both glucose tolerance and insulin secretion in obese, glucose-intolerant mice. These findings demonstrate its antidiabetic potential. |
| Enzyme Assay |
In vitro receptor binding/functional assays for VU0119498 are performed using cells (e.g., CHO cells) expressing human M1, M3, or M5 mAChRs. Cells are loaded with a calcium-sensitive dye and stimulated with a submaximal concentration of acetylcholine in the presence of various concentrations of VU0119498. The potentiation of the calcium response is measured fluorometrically. EC50 values for PAM activity are calculated from dose-response curves.
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| Cell Assay |
Cellular assays for VU0119498 use MIN6-K8 pancreatic β-cells or mouse/human pancreatic islets. Cells are treated with VU0119498 (3-20 µM) in the presence of acetylcholine. Insulin secretion is measured by ELISA or radioimmunoassay. Intracellular calcium levels are measured using a calcium-sensitive dye. These assays confirm the compound's ability to enhance glucose-stimulated insulin secretion.
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| Animal Protocol |
Male WT mice (12 weeks)
0.1, 0.5, 2 mg/kg A single i.p. In vivo animal studies for VU0119498 are conducted in male wild-type mice (12 weeks) or obese, glucose-intolerant mice. VU0119498 is administered as a single intraperitoneal (i.p.) injection at doses of 0.1, 0.5, or 2 mg/kg. Glucose tolerance tests are performed, and insulin secretion is measured. Efficacy is compared to vehicle-treated mice. |
| ADME/Pharmacokinetics |
VU0119498 has a molecular weight of 316.15 g/mol and a molecular formula of C15H10BrNO2. It is an orange to red solid powder. It is typically stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year. It is soluble in DMSO. Pharmacokinetic properties such as oral bioavailability and brain penetration would be determined in preclinical studies.
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| Toxicity/Toxicokinetics |
Preclinical toxicity of VU0119498 would be evaluated in standard toxicology studies. As a PAM of muscarinic receptors, potential adverse effects may include cholinergic side effects such as increased salivation, lacrimation, and gastrointestinal motility. In animal studies, it has shown efficacy in enhancing glucose tolerance at doses of 0.1-2 mg/kg. Comprehensive toxicity data is not widely available.
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| References |
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| Additional Infomation |
VU0119498 is a positive allosteric modulator (PAM) of M1, M3, and M5 muscarinic acetylcholine receptors. It has EC50s of 6.04, 6.38, and 4.08 µM, respectively. It has antidiabetic activity. It is available for research purposes only.
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| Molecular Formula |
C15H10BRNO2
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| Molecular Weight |
316.149403095245
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| Exact Mass |
314.99
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| Elemental Analysis |
C, 56.99; H, 3.19; Br, 25.27; N, 4.43; O, 10.12
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| CAS # |
79183-37-2
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| PubChem CID |
3008304
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| Appearance |
Orange to red solid powder
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
376
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DELLOEULSHGYCG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H10BrNO2/c16-11-7-5-10(6-8-11)9-17-13-4-2-1-3-12(13)14(18)15(17)19/h1-8H,9H2
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| Chemical Name |
1-[(4-bromophenyl)methyl]indole-2,3-dione
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| Synonyms |
VU0119498; VU 0119498; VU-0119498 |
| 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: ~50 mg/mL (~158.2 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 | 3.1631 mL | 15.8153 mL | 31.6306 mL | |
| 5 mM | 0.6326 mL | 3.1631 mL | 6.3261 mL | |
| 10 mM | 0.3163 mL | 1.5815 mL | 3.1631 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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