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| Targets |
Valnivudine targets varicella-zoster virus (VZV) by acting as a prodrug that is converted to its active metabolite, CF-1743. CF-1743 is a bicyclic nucleoside analog (BCNA) that specifically inhibits VZV replication. The exact mechanism of action of BCNAs involves selective phosphorylation by the VZV-encoded thymidine kinase, which is more efficient than phosphorylation by cellular kinases. This selective activation leads to the accumulation of the active triphosphate form in VZV-infected cells, which then inhibits the viral DNA polymerase, thereby blocking viral DNA synthesis and replication. Valnivudine's specificity for VZV over other viruses and host cells is a key feature of its antiviral activity.
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| ln Vitro |
According to in vitro cytotoxicity experiments conducted on rapidly proliferating HepG2 cells, keratinocytes, and normal human primary hepatocytes, the average 50% cytotoxic concentration value of varenivudine (FV-100 free base) was greater than 10 μM [2]. Varicella zoster virus (VZV) is inhibited by CF-1743 (compound 4f) in HEL cells against VZV OKA (EC50=0.3 nM) and VZV YS (EC50=0.1 nM) [3].
In vitro studies have demonstrated that Valnivudine is a potent inhibitor of VZV replication. The active metabolite CF-1743 (compound 4f) has anti-varicella-zoster virus (VZV) activity in HEL cells, with EC50 values of 0.3 nM against VZV OKA and 0.1 nM against VZV YS. In vitro cytotoxicity studies in normal human primary hepatocytes, keratinocytes, and rapidly dividing HepG2 cells have shown that Valnivudine (FV-100 free base) has a mean 50% cytotoxic concentration (CC50) of >10 µM. This indicates a high selectivity index, with potent antiviral activity at sub-nanomolar concentrations and low cytotoxicity at micromolar concentrations. |
| ln Vivo |
In vivo studies have demonstrated that Valnivudine is orally bioavailable and is rapidly and extensively converted to CF-1743 in the body. The compound has been investigated for the treatment of herpes zoster (shingles). However, specific in vivo efficacy data, such as viral load reduction in animal models or clinical trial results, are not detailed in the available literature. Valnivudine's oral bioavailability and potent antiviral activity make it a promising candidate for the treatment of VZV infections. Its development may have been explored for clinical use, but it is not currently approved.
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| Enzyme Assay |
The in vitro assays for Valnivudine measure its antiviral activity against VZV and its cytotoxicity. Antiviral activity is typically assessed using plaque reduction assays or viral replication assays in HEL cells infected with VZV. In these assays, VZV-infected cells are treated with varying concentrations of Valnivudine or its active metabolite CF-1743, and the reduction in viral plaques or viral DNA is measured. The EC50 values for CF-1743 against VZV OKA and VZV YS are 0.3 nM and 0.1 nM, respectively. Cytotoxicity is assessed in normal human primary hepatocytes, keratinocytes, and HepG2 cells using standard cell viability assays such as MTT or CellTiter-Glo. The CC50 for Valnivudine is >10 µM. These assays confirm the potent and selective antiviral activity of Valnivudine.
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| Cell Assay |
In vitro cell-based assays for Valnivudine are conducted using VZV-infected HEL cells or other susceptible cell lines. In a typical assay, cells are infected with VZV and then treated with varying concentrations of Valnivudine or its active metabolite CF-1743. After incubation, viral replication is quantified by measuring the levels of viral DNA by quantitative PCR or by assessing viral plaque formation. The EC50 is determined from dose-response curves. Cytotoxicity is assessed in parallel using uninfected cells to determine the CC50. These cell-based assays confirm that Valnivudine is a potent inhibitor of VZV replication with a high selectivity index.
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| Animal Protocol |
In vivo animal experiments for Valnivudine would typically be conducted in animal models of VZV infection, such as the SCID-hu mouse model or other immunocompromised mouse models that support VZV replication. In a typical study, Valnivudine would be administered orally to infected animals, and viral load in the tissues would be measured over time. The reduction in viral load would be compared to a vehicle control group. However, specific protocols for Valnivudine are not detailed in the available literature. The compound's oral bioavailability makes it suitable for oral administration in these studies. Valnivudine has been investigated in clinical trials for herpes zoster, but the current status of its development is not specified.
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| ADME/Pharmacokinetics |
Valnivudine has a molecular weight of 497.58 g/mol and a molecular formula of C27H35N3O6. It has a density of 1.3±0.1 g/cm³, a boiling point of 667.3±65.0 °C, and a logP of 3.39. The compound is supplied as a light yellow to yellow solid powder. For storage, it is recommended to keep the powder at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 6 months or at -20°C for 1 month. Valnivudine is soluble in DMSO and other organic solvents. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion have been studied, and the compound is known to be rapidly and extensively converted to CF-1743 in vivo.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for Valnivudine is not provided in standard product descriptions. However, in vitro cytotoxicity studies have shown that Valnivudine has a mean 50% cytotoxic concentration (CC50) of >10 µM in normal human primary hepatocytes, keratinocytes, and HepG2 cells. This indicates a favorable safety profile in vitro, with a high selectivity index relative to its potent antiviral activity. In clinical studies, Valnivudine has been investigated for the treatment of herpes zoster, and its safety profile would have been evaluated. However, specific toxicity data, such as LD50 or organ toxicity, are not detailed in the available literature. As with all research chemicals, standard laboratory safety precautions should be followed when handling Valnivudine.
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| References |
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| Additional Infomation |
Valnivudine (FV-100 free base) is a research compound that has been investigated for the treatment of herpes zoster (shingles). It is an orally bioavailable prodrug of CF-1743, a bicyclic nucleoside analog (BCNA) with highly specific antiviral activity against varicella-zoster virus (VZV). Valnivudine is rapidly and extensively converted to CF-1743 in vivo. The active metabolite CF-1743 exhibits potent anti-VZV activity, with EC50 values of 0.3 nM against VZV OKA and 0.1 nM against VZV YS in HEL cells. Valnivudine's mechanism of action involves selective phosphorylation by the VZV-encoded thymidine kinase, leading to inhibition of viral DNA synthesis. The compound has been studied as a potential therapy for shingles, but it is not currently approved for clinical use.
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| Molecular Formula |
C27H35N3O6
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| Molecular Weight |
497.592
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| Exact Mass |
497.252
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| CAS # |
956483-02-6
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| Related CAS # |
Valnivudine hydrochloride;956483-03-7
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| PubChem CID |
16063377
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
667.3±65.0 °C at 760 mmHg
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| Flash Point |
357.4±34.3 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.624
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| LogP |
3.39
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
36
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| Complexity |
905
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CCCCCC1=CC=C(C=C1)C2=CC3=CN(C(=O)N=C3O2)[C@H]4C[C@@H]([C@H](O4)COC(=O)[C@H](C(C)C)N)O
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| InChi Key |
FJRRWJMFUNGZBJ-RBVMOCNTSA-N
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| InChi Code |
InChI=1S/C27H35N3O6/c1-4-5-6-7-17-8-10-18(11-9-17)21-12-19-14-30(27(33)29-25(19)36-21)23-13-20(31)22(35-23)15-34-26(32)24(28)16(2)3/h8-12,14,16,20,22-24,31H,4-7,13,15,28H2,1-3H3/t20-,22+,23+,24-/m0/s1
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| Chemical Name |
[(2R,3S,5R)-3-hydroxy-5-[2-oxo-6-(4-pentylphenyl)furo[2,3-d]pyrimidin-3-yl]oxolan-2-yl]methyl (2S)-2-amino-3-methylbutanoate
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| Synonyms |
FV100 FV-100 FV 100Valnivudine
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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) |
DMSO : ~50 mg/mL (~100.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.02 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0097 mL | 10.0484 mL | 20.0969 mL | |
| 5 mM | 0.4019 mL | 2.0097 mL | 4.0194 mL | |
| 10 mM | 0.2010 mL | 1.0048 mL | 2.0097 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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