| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
AV5124 is the orally bioavailable prodrug of AV5116, which targets the influenza virus cap-dependent endonuclease (CEN) within the PA subunit. CEN is essential for viral RNA transcription, as it cleaves the 5‘ cap from host pre-mRNAs to prime viral mRNA synthesis. Inhibition of CEN blocks viral replication. AV5116, the active metabolite, shows superior activity against clinically prevalent I38T PA resistance mutants compared to baloxavir acid. AV5124 delivers the active AV5116, which has a thiophene substitution in the bulky hydrophobic group (BHG), conferring key differential activity against baloxavir-resistant variants.
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| ln Vitro |
In vitro, AV5116 (the active metabolite) shows approximately 7.9-fold lower EC₅0 in plaque reduction assays compared to baloxavir acid against I38T mutant influenza viruses. AV5116 inhibits influenza A and B virus polymerase complexes and viral replication at nanomolar concentrations, demonstrating activity against both oseltamivir-susceptible and oseltamivir-resistant strains. Documented mitochondrial safety (CC₅0Glu/CC₅0Gal ≤ 1) and a clean 44-target off-target profile support its selectivity.
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| ln Vivo |
AV5124 protected 60% of animals from mortality at a dose of 20 mg/kg, and completely protected mice from virus-induced mortality at a dose of 50 mg/kg.
In vivo, AV5124 (50 mg/kg) completely protected mice from virus-induced mortality, and at 20 mg/kg, it protected 60% of animals from mortality in a lethal challenge model where baloxavir marboxil (BXM) failed to fully clear the virus. It delivers 23.9% oral bioavailability, with a 24-fold lung-to-plasma Cmax ratio, ensuring high drug concentrations at the site of infection. The compound is a promising research-grade antiviral agent but is not an FDA-approved drug. |
| Enzyme Assay |
In vitro cap-dependent endonuclease (CEN) inhibition assay: The activity of recombinant influenza A (H1N1) PA-N-terminal domain (PA-Nter, residues 1-209) is measured using a fluorescence-based assay. The enzyme (0.1-1 uM) is incubated in assay buffer (50 mM Tris-HCl pH 7.5, 100 mM NaCl, 10 mM MgCl2, 10 mM DTT, 0.1% BSA) with a fluorogenic RNA substrate (e.g., 5‘-FAM- dT10-3'-BHQ1) and varying concentrations of AV5116 (0.001-1000 nM). Fluorescence is measured at λex 495 nm, λem 520 nm for 30-60 min. IC₅0 values are calculated. For antiviral activity, plaque reduction assays are performed using MDCK cells.
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| Cell Assay |
For antiviral activity, MDCK cells are seeded in 6-well plates (5×10⁵ cells/well) and infected with influenza A or B virus (MOI 0.001-0.01). AV5116 (the active metabolite) or AV5124 (prodrug) is added at concentrations of 0.01-1000 nM. After 48-72 h, viral titers are quantified by plaque assay. The EC₅0 is calculated. Cytotoxicity is assessed by MTT assay in uninfected cells. The CC₅0 is determined, and the selectivity index (SI = CC₅0/EC₅0) is calculated. AV5116 shows low cytotoxicity.
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| Animal Protocol |
In vivo efficacy is evaluated in a lethal mouse challenge model. Female BALB/c mice (6-8 weeks old, n=10/group) are intranasally infected with a lethal dose of influenza A virus (e.g., A/PR/8/34 H1N1, 2-5× LD₅0, 25 uL). AV5124 is formulated in 10% DMSO + 5% Tween 80 + 85% saline and administered orally (gavage) at doses of 10-50 mg/kg, 2-6 h post-infection, once daily for 5-7 days. Control groups receive vehicle alone or baloxavir marboxil (10 mg/kg). Survival is monitored for 14-21 days. Body weight is measured daily. Lung viral titers are measured by plaque assay at day 3-5 post-infection. AV5124 (20 mg/kg) protects 60% of animals; (50 mg/kg) completely protects from mortality.
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| ADME/Pharmacokinetics |
AV5124 is an orally bioavailable prodrug with an oral bioavailability of 23.9% in preclinical models. After oral administration, it is rapidly converted to the active metabolite AV5116. The lung-to-plasma Cmax ratio is 24-fold, indicating high lung accumulation. The elimination half-life in mice is expected to be 4-8 hours. For research use, it is stored as a powder at -20degC (powder: -20degC for 3 years, 4degC for 2 years; in solvent: -80degC for 6 months, -20degC for 1 month), protected from light and moisture. It is soluble in DMSO (10 mM).
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| Toxicity/Toxicokinetics |
AV5124 has low cytotoxicity in vitro, with a clean off-target profile. Documented mitochondrial safety (CC₅0Glu/CC₅0Gal ≤ 1) indicates minimal risk of mitochondrial toxicity. In lethal mouse challenge models, AV5124 was well-tolerated at doses up to 50 mg/kg. For research use, standard safety precautions for handling research chemicals apply: use PPE (gloves, lab coat, safety goggles), work in a fume hood, avoid inhalation and skin contact. Not for human consumption.
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| References | |
| Additional Infomation |
AV5124 (tivoxavir marboxil; TRX-100; CAS# 2417851-93-3) is a research-grade, second-generation, orally bioavailable influenza virus cap-dependent endonuclease (CEN) inhibitor. It is not an FDA-approved drug (baloxavir marboxil is approved). It is used to study influenza virus replication, drug resistance (I38T mutants), and as a potential antiviral agent for pandemic preparedness. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C25H21F2N3O7S2
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|---|---|
| Molecular Weight |
577.58
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| Exact Mass |
577.079
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| CAS # |
2417851-93-3
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| PubChem CID |
155280058
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| Appearance |
White to off-white solid powder
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| Density |
1.63±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)
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| Boiling Point |
720.8±70.0 °C(Predicted)
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| LogP |
0
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
39
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| Complexity |
1080
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC(=O)OCOC1=C2C(=O)N3CCOC[C@H]3N(N2C=CC1=O)[C@H]4C5=C(CSC6=C4SC=C6)C(=C(C=C5)F)F
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| InChi Key |
JFAAVTYPCCKWCW-QUCCMNQESA-N
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| InChi Code |
InChI=1S/C25H21F2N3O7S2/c1-34-25(33)37-12-36-22-16(31)4-6-29-21(22)24(32)28-7-8-35-10-18(28)30(29)20-13-2-3-15(26)19(27)14(13)11-39-17-5-9-38-23(17)20/h2-6,9,18,20H,7-8,10-12H2,1H3/t18-,20+/m1/s1
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| Chemical Name |
[(3R)-2-[(10S)-6,7-difluoro-5,10-dihydrothieno[3,2-c][2]benzothiepin-10-yl]-9,12-dioxo-5-oxa-1,2,8-triazatricyclo[8.4.0.03,8]tetradeca-10,13-dien-11-yl]oxymethyl methyl carbonate
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.7314 mL | 8.6568 mL | 17.3136 mL | |
| 5 mM | 0.3463 mL | 1.7314 mL | 3.4627 mL | |
| 10 mM | 0.1731 mL | 0.8657 mL | 1.7314 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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