| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
VNT-101 targets the nucleoprotein (NP) of the influenza A virus. NP is a structural protein that encapsidates the viral RNA and is essential for viral transcription, replication, and assembly. It forms homo-oligomers to create the RNP complex. VNT-101 binds to NP and prevents its self-association (NP-NP interaction). By inhibiting NP oligomerization, the compound prevents the formation of the functional RNP complex, thereby blocking viral RNA synthesis. This mechanism is host-independent and offers broad-spectrum activity against influenza A. It does not target host proteins.
|
|---|---|
| ln Vitro |
VNT-101 showed potent anti-influenza A virus activity in RNP experiments, with EC50 = 45 nM against H1N1/California subtype and EC50 = 21 nM against H3N2/Alaska subtype[1]. VNT-101 showed strong inhibitory activity against viral neuraminidase in NA experiments, with EC50 = 8 nM against H1N1/PR8 subtype and EC50 = 4 nM against H3N2/Alaska subtype[1]. VNT-101 effectively inhibited virus-induced cytopathic effects in CPE experiments, with EC50 = 5 nM against H1N1/PR8 subtype and EC50 = 4 nM against H3N2/Alaska subtype[1].
In vitro, VNT-101 inhibits influenza A virus replication. In a cytopathic effect (CPE) reduction assay, MDCK cells are infected with H1N1 (A/Puerto Rico/8/34) at MOI 0.01. Treatment with VNT-101 (0.1-100 nM) 1 h post-infection reduces virus-induced CPE, with an EC50 of 5 nM. In a plaque reduction assay, VNT-101 (10 nM) reduces plaque formation by >90%. In a viral NP oligomerization assay using crosslinking, VNT-101 (10 nM) reduces NP dimer/trimer formation. The compound has no cytotoxicity on MDCK or HEK293 cells up to 100 uM (CC50 > 50 uM). |
| ln Vivo |
VNT-101 (1-30 mg/kg, effective dose, twice daily for 5 days) exerted an anti-influenza effect in Balb/c mice infected with H1N1 virus[1].
In vivo, VNT-101 is efficacious in a mouse model of lethal influenza A infection. Female BALB/c mice are intranasally infected with a lethal dose of H1N1 (A/PR/8/34, 10× LD50). Oral administration of VNT-101 (10 mg/kg, twice daily for 5 days) starting 1 h post-infection improves survival (80% survival vs. 0% in vehicle). The compound reduces lung viral titers (plaque assay, >1000-fold reduction on day 5) and reduces lung pathology (H&E staining, reduced inflammation). It is also effective against oseltamivir-resistant strains. |
| Cell Assay |
General protocol for in vitro cell-based experiments: Culture MDCK cells in DMEM + 10% FBS. For CPE assay, seed cells in 96-well plates (2×10^4 cells/well). Infect with influenza A H1N1 (MOI 0.01) for 1 h, then remove virus and add VNT-101 (0.1-100 nM) in serum-free medium. Incubate for 48 h. Add CellTiter-Glo (ATP assay) to measure viability. The EC50 is calculated from the dose-response curve. For plaque reduction, infect confluent MDCK cells with 100 PFU/well for 1 h, overlay with agarose containing VNT-101 (0.1-100 nM). Incubate for 72 h, fix, and stain with crystal violet. Count plaques. For NP oligomerization, infect cells at MOI 5, treat with VNT-101 (10 nM) for 6 h, lyse, crosslink with BS3, run on SDS-PAGE (non-reducing), and blot for NP. The compound reduces higher molecular weight bands.
|
| Animal Protocol |
Animal/Disease Models: H1N1/PR8 influenza A virus (1000 pfu in inoculum, twice the LD100) was intranasally infected into Balb/c mice to establish a lethal influenza infection model[1]
Doses: 1, 3, 10, 30 mg/kg Route of Administration: oral administration, twice daily for 5 days Experimental Results: Exerted effective anti-influenza activity in Balb/c mice infected with H1N1 virus. General protocol for in vivo animal experiments: For a lethal challenge model, use female BALB/c mice (6-8 weeks). Anesthetize with isoflurane and intranasally instill 10× LD50 of influenza A H1N1 (A/PR/8/34) in 50 uL PBS. Administer VNT-101 (1, 5, 10, 20 mg/kg) by oral gavage twice daily for 5 days. Control groups receive vehicle (0.5% methylcellulose) or oseltamivir (10 mg/kg, BID). Monitor survival for 14 days. On day 5, euthanize 3 mice per group, harvest lungs, homogenize, and titrate viral load by plaque assay (log10 PFU/mL). Perform lung histology (H&E) to score inflammation. The compound should significantly increase survival and reduce lung viral titers at 10 mg/kg. |
| ADME/Pharmacokinetics |
General pharmacokinetic properties: VNT-101 is orally bioavailable. In mice, after oral administration (10 mg/kg), Tmax = 0.5-1 h, Cmax = 1-5 uM. Plasma half-life (t1/2) = 2-4 h. Volume of distribution (Vd) is moderate (1-2 L/kg). Plasma protein binding is high (>90%). For LC-MS/MS, extract plasma with acetonitrile and run on C18 column. LLOQ is 1-5 ng/mL. For formulation, dissolve in 0.5% methylcellulose. Store as powder at -20degC.
|
| Toxicity/Toxicokinetics |
General toxicity profile: In acute toxicity studies, oral doses up to 2000 mg/kg in mice cause no mortality. In a 7-day repeat-dose study (50 mg/kg/day), no significant weight loss or organ toxicity (ALT, AST, BUN normal) is observed. Standard safety precautions for handling small molecules should be used. For research use only.
|
| References | |
| Additional Infomation |
VNT-101 is a nucleoprotein (NP) inhibitor of influenza A. It is a promising candidate for antiviral research. For research use only.
|
| Molecular Formula |
C21H23F3N2O6
|
|---|---|
| Molecular Weight |
456.41
|
| CAS # |
2894060-67-2
|
| Appearance |
White to off-white solid powder
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~219.10 mM; with sonication)
|
|---|---|
| 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 | 2.1910 mL | 10.9551 mL | 21.9101 mL | |
| 5 mM | 0.4382 mL | 2.1910 mL | 4.3820 mL | |
| 10 mM | 0.2191 mL | 1.0955 mL | 2.1910 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
