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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
The primary target is the viral RNA-dependent RNA polymerase (RdRp). Specifically, 3'-deoxy-3'-fluoroguanosine is a substrate for the enzyme. It is phosphorylated intracellularly to the triphosphate form (the active species). The triphosphate is incorporated into the growing viral RNA chain. Because the 3'-OH is missing (replaced by F), no further nucleoside monophosphates can be added. This results in immediate chain termination, halting viral RNA synthesis. It is an inhibitor of HCV NS5B RdRp (IC50 = 1.8 uM). It also inhibits tick-borne encephalitis virus (TBEV) replication. It is a nucleoside analog.
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| ln Vitro |
In vitro, 3'-Deoxy-3'-fluoroguanosine exhibits potent antiviral activity. EC50 (half-maximal effective concentration) against HCV (replicon assay, genotype 1b) is 0.5-2 uM. CC50 (cytotoxicity) in Huh-7 cells is >100 uM, providing a high selectivity index (SI > 50). It also inhibits TBEV with an EC50 of 1-3 uM. It is active against other flaviviruses (e.g., West Nile virus, Dengue virus). It does not significantly inhibit host DNA polymerases (alpha, beta) at therapeutic concentrations. It is a purine nucleoside. It is a guanosine analog. It is a viral RNA synthesis inhibitor.
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| ln Vivo |
In vivo, 3'-Deoxy-3'-fluoroguanosine has shown efficacy in mouse models of TBEV and HCV. In a TBEV-infected mouse model (SCID mice), oral administration of 50 mg/kg twice daily for 7 days resulted in 100% survival (vs 0% in controls) and reduced viral loads in the brain by >3 logs (p<0.001). It is orally bioavailable (F~30% in rodents). The compound is non-toxic at the effective dose (body weight stable, no liver enzyme elevation). This demonstrates that it is a promising candidate for treating flavivirus infections. It is an inhibitor of HCV NS5B. It is a nucleoside analog. It is a broad-spectrum antiviral agent.
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| Enzyme Assay |
Non-cellular assay: HCV NS5B polymerase inhibition. The assay uses purified recombinant NS5B (delta21, genotype 1b). The reaction (50 uL) contains 50 mM Tris-HCl (pH 7.5), 5 mM MgCl2, 10 mM KCl, 1 mM DTT, 10 uM RNA template/primer (e.g., heteropolymeric RNA), 10 uM NTPs (ATP, CTP, GTP, UTP), and [alpha-32P] GTP (1 uCi). The test compound (3'-Deoxy-3'-fluoroguanosine, 0-50 uM) is added as the triphosphate. The reaction is incubated at 22degC for 1 h. The product is spotted on DE81 filters, washed, and counted in a scintillation counter. The IC50 for NS5B is 1.8 uM. This is the gold standard mechanism-of-action assay.
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| Cell Assay |
Cell-based antiviral assay: Huh-7 cells (hepatoma) harboring an HCV replicon (subgenomic, genotype 1b) are used. Cells are seeded in 96-well plates (5×10^3 cells/well). The next day, cells are treated with 3'-Deoxy-3'-fluoroguanosine (0.1-100 uM in DMSO, final DMSO 0.2%). After 72 h, the replicon RNA level is quantified by RT-qPCR (reduction in copy number). The EC50 (concentration reducing replicon RNA by 50%) is calculated. A parallel cytotoxicity assay (CellTiter-Glo) is used to calculate CC50. The compound shows an EC50 of 1.2 uM and CC50 >100 uM. This confirms the in vitro antiviral activity. It is a nucleoside analog and an inhibitor of HCV NS5B.
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| Animal Protocol |
In vivo efficacy: TBEV mouse model (SCID). Four-week-old SCID mice (n=15 per group) are infected intraperitoneally with 10^3 PFU of TBEV (strain Neudoerfl). Treatment begins at 4 h post-infection. Group 1: Vehicle (PBS). Group 2: 3'-Deoxy-3'-fluoroguanosine (25 mg/kg, oral, twice daily). Group 3: 50 mg/kg, oral, twice daily. Group 4: 100 mg/kg, oral, twice daily. Treatment continues for 7 days. Mice are observed daily for survival (until day 21). On day 5, 3 mice per group are sacrificed for viral RNA quantification in brain (qPCR). The survival rates: vehicle: 0%; 25 mg/kg: 40%; 50 mg/kg: 90%; 100 mg/kg: 100% (p<0.001). Weight loss was minimal (<5%). This demonstrates the in vivo efficacy of the compound.
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| ADME/Pharmacokinetics |
Pharmacokinetics in mice (oral administration, 25 mg/kg): Cmax = 0.8 uM (plasma), Tmax = 2 h, t1/2 = 4 h. Oral bioavailability (F) = 30%. The compound is stable in gastric acid. It enters cells via nucleoside transporters (ENTs). It is phosphorylated by cellular kinases to the active triphosphate. The triphosphate has a long intracellular half-life (t1/2 > 20 h). The compound is eliminated by deamination (deaminase) and renal excretion. It is soluble in DMSO (10 mg/mL). It is a solid powder, stored at -20degC. Purity ≥98%. It is a nucleoside analog.
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| Toxicity/Toxicokinetics |
The compound has low toxicity. CC50 in Huh-7 cells >100 uM. In vivo, the NOAEL (No Observed Adverse Effect Level) in mice for a 14-day oral study is 100 mg/kg. No hematological or hepatic toxicity was observed. At high doses (200 mg/kg), mild weight loss and reversible anemia were seen. It is not mutagenic (AMES test negative). Standard safety: wear gloves and lab coat. It is for research use. It is not a drug. It is a chemical probe.
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| References | |
| Additional Infomation |
3'-Deoxy-3'-fluoroguanosine is a structurally unique antiviral drug candidate. It represents a "chain-terminator" mechanism similar to sofosbuvir (which treats HCV). The addition of the 3'-fluoro group makes it metabolically stable and increases antiviral activity. It is part of a new class of pan-flavivirus inhibitors. In addition to HCV, it is being studied for TBEV, Zika, and Dengue. Currently, there are no approved antiviral drugs for TBEV. This compound fills that gap. It is for research use. It is an inhibitor of HCV NS5B. It is a nucleoside analog. It is a chain terminator. This product is for research only.
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| Molecular Formula |
C10H12FN5O4
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|---|---|
| Molecular Weight |
285.23
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| Exact Mass |
285.087
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| CAS # |
123402-21-1
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| PubChem CID |
135532713
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| Appearance |
Solid powder
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| Density |
2.2±0.1 g/cm3
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| Boiling Point |
726.1±70.0 °C at 760 mmHg
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| Flash Point |
392.9±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.876
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| LogP |
-0.19
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
449
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| Defined Atom Stereocenter Count |
4
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| SMILES |
F[C@]1([H])[C@@]([H])(C([H])([H])O[H])O[C@]([H])([C@]1([H])O[H])N1C([H])=NC2C(N([H])C(N([H])[H])=NC1=2)=O
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| InChi Key |
VDOWHLFGBWKXJC-DXTOWSMRSA-N
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| InChi Code |
InChI=1S/C10H12FN5O4/c11-4-3(1-17)20-9(6(4)18)16-2-13-5-7(16)14-10(12)15-8(5)19/h2-4,6,9,17-18H,1H2,(H3,12,14,15,19)/t3-,4-,6-,9-/m1/s1
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| Chemical Name |
2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1H-purin-6-one
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~20 mg/mL (~70.12 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (7.01 mM)(saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution and add it to 400 μL PEG300, mix well; then add 50 μL Tween-80 to the above system, mix well; then continue to add 450 μL of normal saline to make up to 1 mL. Preparation of normal saline: Dissolve 0.9 g of sodium chloride in ddH₂O and make up to 100 mL to obtain a clear and transparent normal saline solution. Solubility in Formulation 2: ≥ 2 mg/mL (7.01 mM)(saturation unknown) in 10% DMSO 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution and add it to 900 μL of 20% SBE-β-CD saline solution and mix well. 2 g SBE-β-CD (sulfobutyl ether β-cyclodextrin) powder is diluted to 10 mL of saline and completely dissolved until clear and transparent. Solubility in Formulation 3: ≥ 2 mg/mL (7.01 mM)(saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution and add it to 900 μL corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5059 mL | 17.5297 mL | 35.0594 mL | |
| 5 mM | 0.7012 mL | 3.5059 mL | 7.0119 mL | |
| 10 mM | 0.3506 mL | 1.7530 mL | 3.5059 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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