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| 1mg |
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| Targets |
Picornavirus 3C protease. AG-7404 is an irreversible inhibitor of the 3C cysteine protease, a viral enzyme essential for the proteolytic processing of the viral polyprotein into functional mature proteins. By covalently binding to the active site cysteine residue, AG-7404 blocks protease activity, preventing the generation of viral capsid and polymerase proteins, and effectively halts viral replication. It does not directly target host cell proteins.
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| ln Vitro |
AG-7404 inhibits picornaviral 3C protease, with anti-poliovirus activity (EC50 = 0.080-0.674 uM). It is fully active against all V-073-resistant variants with EC50 values ranging from 0.218-0.819 uM. AG-7404 has synergistic antiviral activity with capsid inhibitors such as V-073 (Pocapavir) or BTA798 (Vapendavir). It is an irreversible inhibitor, with activity against a broad panel of poliovirus strains.
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| ln Vivo |
No specific in vivo data has been reported for AG-7404 alone. As an orally active 3C protease inhibitor, it would be evaluated in animal models of enterovirus infection. For poliovirus, a transgenic mouse model expressing the human poliovirus receptor (PVR) is used. Mice would be infected with poliovirus via intracranial or intraperitoneal injection, and then treated orally with AG-7404 (10-100 mg/kg, twice daily) for 5-7 days. Survival, clinical scores (paralysis), and viral titers in spinal cord and brain would be assessed.
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| Enzyme Assay |
AG-7404 is an irreversible inhibitor of picornavirus 3C protease. For cell-free inhibition assays, purified recombinant 3C protease (e.g., from poliovirus or rhinovirus) is incubated with varying concentrations of AG-7404 (0.1 nM-100 uM) in assay buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 1 mM DTT, 1 mM EDTA) for 15-60 minutes at room temperature. A fluorogenic peptide substrate (e.g., Dabcyl-RTLEVFTF-EDANS) is added, and fluorescence is measured at excitation 340 nm and emission 490 nm for 30-60 minutes. IC50 is determined from the decrease in reaction rate, and irreversible binding is confirmed by dilution or dialysis experiments.
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| Cell Assay |
For in vitro antiviral assays, HeLa or RD cells are seeded in 96-well plates at 1×10⁴ cells/well. Cells are infected with poliovirus (e.g., Mahoney strain, MOI 0.01-0.1) and simultaneously treated with AG-7404 at concentrations ranging from 0.01-100 uM. After 24-48 hours, viral cytopathic effect (CPE) is assessed by MTT assay or by crystal violet staining. The 50% effective concentration (EC50) for inhibition of CPE is calculated. For confirmatory studies, viral RNA is extracted from culture supernatants and quantified by RT-qPCR.
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| Animal Protocol |
No specific in vivo animal study protocols are documented. For enterovirus antiviral testing, a typical protocol uses 6-8 week old transgenic mice expressing the human poliovirus receptor (TgPVR mice). Mice are challenged intraperitoneally with 10⁵-10⁶ PFU of poliovirus (e.g., Mahoney or Sabin strain) and then treated orally with AG-7404 at doses of 20-50 mg/kg, twice daily for 5 days. Survival is monitored daily for 14-21 days. For neurovirulence assessment, mice are observed for flaccid paralysis. Spinal cord and brain stem are harvested for viral titer measurement by plaque assay.
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| ADME/Pharmacokinetics |
AG-7404 is an orally active small molecule with favorable oral bioavailability. While specific PK parameters are not fully published for AG-7404, related 3C protease inhibitors typically exhibit moderate half-lives (2-6 hours) in rodents. It is likely metabolized by CYP3A4 in the liver. The compound has good oral absorption, enabling therapeutic concentrations to be achieved in plasma and tissues.
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| Toxicity/Toxicokinetics |
No specific toxicity data has been reported. As an irreversible inhibitor of a viral protease, the compound is not expected to have significant off-target effects at therapeutic doses, but this has not been formally evaluated. Safety pharmacology studies (CYP inhibition, hERG, genotoxicity) have not been published. The compound is for research use only.
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| References | |
| Additional Infomation |
AG-7404 has the molecular formula C26H29N5O7 and a molecular weight of 523.54. The IUPAC name is ethyl (S,E)-4-((S)-2-(3-(5-methylisoxazole-3-carboxamido)-2-oxopyridin-1(2H)-yl)pent-4-ynamido)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate. It is also known as AG-7404, V-7404, AG7404, and V7404. It has been studied for the treatment of poliovirus and enterovirus infections but is not approved for clinical use.
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| Molecular Formula |
C26H29N5O7
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|---|---|
| Exact Mass |
523.21
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| Elemental Analysis |
C, 59.65; H, 5.58; N, 13.38; O, 21.39
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| CAS # |
343565-99-1
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| PubChem CID |
5280053
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| Appearance |
Solid powder
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| LogP |
0.9
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
38
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| Complexity |
1090
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CCOC(=O)/C=C/[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC#C)N2C=CC=C(C2=O)NC(=O)C3=NOC(=C3)C
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| InChi Key |
QCUZOJBYWQPLIN-BNMFZAHFSA-N
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| InChi Code |
InChI=1S/C26H29N5O7/c1-4-7-21(31-13-6-8-19(26(31)36)29-24(34)20-14-16(3)38-30-20)25(35)28-18(9-10-22(32)37-5-2)15-17-11-12-27-23(17)33/h1,6,8-10,13-14,17-18,21H,5,7,11-12,15H2,2-3H3,(H,27,33)(H,28,35)(H,29,34)/b10-9+/t17-,18+,21-/m0/s1
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| Chemical Name |
(S,E)-ethyl 4-((S)-2-(3-(5-methylisoxazole-3-carboxamido)-2-oxopyridin-1(2H)-yl)pent-4-ynamido)-5-((S)-2-oxopyrrolidin-3-yl)pent-2-enoate
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| Synonyms |
AG-7404; AG 7404; AG7404; V 7404; V-7404; V7404;
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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 |
| 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.) |
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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