| Size | Price | Stock | Qty |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target of cap-dependent endonuclease-IN-1 is the PA endonuclease domain of the influenza virus polymerase complex. By inhibiting the endonuclease activity, the compound prevents the cleavage of host mRNA caps, a critical step in viral transcription (cap-snatching). This inhibition blocks viral mRNA synthesis and replication. The compound targets a conserved site in the PA endonuclease domain, which may provide activity against multiple influenza strains.
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| ln Vitro |
In vitro studies have demonstrated the antiviral activity of cap-dependent endonuclease-IN-1 against influenza viruses. The compound inhibits the endonuclease activity of the PA subunit in biochemical assays. In cell culture, the compound inhibits influenza virus replication, with EC₅₀ values in the low nanomolar to low micromolar range. The compound may be active against both influenza A and B viruses. Specific potency data have been reported in the antiviral literature.
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| ln Vivo |
In vivo efficacy of cap-dependent endonuclease-IN-1 has been evaluated in animal models of influenza infection. Mouse models have been used to assess the compound's ability to reduce viral titers, improve clinical signs, and increase survival. The compound may be administered via oral, intranasal, or intraperitoneal routes. Specific in vivo data have been reported in the literature. Further studies are needed to confirm its therapeutic potential and to optimize dosing regimens.
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| Enzyme Assay |
For endonuclease inhibition assays, recombinant influenza PA endonuclease domain is incubated with a fluorescently labeled RNA substrate in the presence of cap-dependent endonuclease-IN-1. The cleavage of the substrate is monitored by fluorescence polarization or gel electrophoresis. IC₅₀ values are calculated from dose-response curves. For binding studies, surface plasmon resonance or other biophysical techniques may be used.
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| Cell Assay |
For in vitro cell-based studies, MDCK cells are infected with influenza virus and treated with serial dilutions of cap-dependent endonuclease-IN-1. Antiviral activity is assessed by measuring viral RNA by RT-qPCR, viral protein expression by immunofluorescence, or infectious virus production by plaque or TCID₅₀ assay. Cytotoxicity is assessed in parallel using standard cell viability assays. Time-of-addition studies may be performed to determine the stage of the viral life cycle affected.
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| Animal Protocol |
In vivo animal studies for influenza antivirals typically use mouse models. Mice are infected intranasally with influenza virus and treated with cap-dependent endonuclease-IN-1 via oral, intranasal, or intraperitoneal routes, often starting before or shortly after infection. Efficacy endpoints include survival, weight loss, clinical score, and viral load in lung tissue. Pharmacokinetic sampling may be included. Standard protocols for influenza efficacy studies are described in the literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of cap-dependent endonuclease-IN-1 have been characterized as part of preclinical development. As a small molecule, it is expected to have properties suitable for the intended route of administration. Specific PK parameters such as half-life, clearance, volume of distribution, oral bioavailability, and protein binding have been reported. The compound's metabolism and elimination pathways have also been studied. PK/PD relationships may be evaluated to guide dosing.
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| Toxicity/Toxicokinetics |
Toxicological data for cap-dependent endonuclease-IN-1 have been generated as part of preclinical safety assessment. Standard toxicology studies including acute toxicity, repeated-dose toxicity, genotoxicity, and safety pharmacology have been conducted. The compound's safety profile in animal models has been evaluated. Specific toxicity data such as NOAEL and target organ toxicity have been reported. Comprehensive toxicological evaluation is essential for clinical development.
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| References | |
| Additional Infomation |
Cap-dependent endonuclease-IN-1 is a research compound for influenza antiviral drug discovery targeting the cap-snatching mechanism. This mechanism is the target of approved influenza drugs such as baloxavir marboxil. The compound represents a potential lead for the development of new influenza therapeutics, particularly for strains resistant to neuraminidase inhibitors. No clinical trials have been reported for this specific compound. Further development would require extensive preclinical and clinical evaluation.
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| Molecular Formula |
C27H22F2N2O6S
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|---|---|
| Exact Mass |
540.116
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| CAS # |
2365473-17-0
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| PubChem CID |
139338844
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.6
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
38
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| Complexity |
1060
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC(=O)OCOC1=C2C(=O)C3(CC3)CN(N2C=CC1=O)[C@H]4C5=C(CSC6=CC=CC=C46)C(=C(C=C5)F)F
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| InChi Key |
XNCHLCOISMLPJG-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C27H22F2N2O6S/c1-35-26(34)37-14-36-24-19(32)8-11-30-23(24)25(33)27(9-10-27)13-31(30)22-15-6-7-18(28)21(29)17(15)12-38-20-5-3-2-4-16(20)22/h2-8,11,22H,9-10,12-14H2,1H3/t22-/m0/s1
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| Chemical Name |
[1-[(11S)-7,8-difluoro-6,11-dihydrobenzo[c][1]benzothiepin-11-yl]-4,6-dioxospiro[2H-pyrido[1,2-b]pyridazine-3,1'-cyclopropane]-5-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 |
| 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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