| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Valopicitabine HCl targets the HCV NS5B polymerase, which is the viral RNA-dependent RNA polymerase essential for HCV replication. As a prodrug, it is metabolized to the active nucleoside analog NM107, which competitively inhibits NS5B polymerase, causing chain termination. This mechanism is specific to the viral polymerase, making it a selective antiviral agent.
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|---|---|
| ln Vitro |
In vitro, Valopicitabine is a potent anti-HCV agent. Its active metabolite, 2'-C-methylcytidine (NM107), competitively inhibits NS5B polymerase, leading to chain termination of viral RNA synthesis. The compound demonstrates potent antiviral activity against HCV in cell-based replication assays.
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| ln Vivo |
The Cmax, AUC, t1/2, and tmax values of valopitabine (NM283) (100 mg/kg; oral; Sprague-Dawley rats) were 0.64, 8.95 μg h/mL, 3.624 μg/mL, and t1/2, respectively. one hour and thirty minutes[2].
In vivo, Valopicitabine has potent antiviral activity against chronic hepatitis C virus genotype-1 in the chimpanzee. In Sprague-Dawley rats, following oral administration at 100 mg/kg, it exhibits moderate Cmax (3.62 μg/mL) and a terminal elimination half-life (T1/2) of 0.64 h. |
| Enzyme Assay |
In vitro enzyme assays for Valopicitabine HCl are performed using purified HCV NS5B polymerase. The enzyme is incubated with a RNA template, nucleotides, and the active metabolite NM107. The incorporation of radiolabeled nucleotides into the growing RNA chain is measured, and the inhibition of polymerase activity is quantified. IC50 values are calculated from concentration-response curves.
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| Cell Assay |
In vitro cellular assays for Valopicitabine HCl are performed using HCV replicon cell lines. Cells are treated with the compound at various concentrations, and viral RNA replication is measured by quantifying HCV RNA levels using quantitative RT-PCR or by measuring reporter gene expression. The EC50 for inhibition of HCV replication is calculated from concentration-response curves.
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| Animal Protocol |
In vivo animal experiments for Valopicitabine HCl are conducted in chimpanzee models of chronic hepatitis C virus genotype-1 infection. A typical protocol involves oral administration of the compound, followed by assessment of viral load reduction, liver enzyme levels, and pharmacokinetic parameters. Efficacy is evaluated by measuring the decline in HCV RNA levels in serum.
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| ADME/Pharmacokinetics |
Valopicitabine HCl exhibits moderate Cmax (3.62 μg/mL) and terminal elimination half-life (T1/2 0.64 h) following oral administration (100 mg/kg) in Sprague-Dawley rats. As a prodrug, it is orally bioavailable and is converted to the active metabolite 2'-C-methylcytidine (NM107).
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| Toxicity/Toxicokinetics |
The toxicity profile of Valopicitabine HCl has been evaluated in preclinical studies. As a nucleoside analog, its safety profile is characterized by its effects on mitochondrial function and potential for hematological toxicity. Specific toxicity data, including organ-specific effects and dose-limiting toxicities, are available from preclinical toxicology studies supporting its development.
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| References | |
| Additional Infomation |
Valopicitabine hydrochloride is the dihydrochloride of Valopicitabine, a 3-O-valine ester prodrug of the nucleoside analog 2'-C-methylcytidine, which possesses anti-hepatitis C virus (HCV) activity. After administration, Valopicitabine is converted to 2'-C-methylcytidine; this metabolite, upon phosphorylation to its 5-triphosphate form, inhibits viral RNA chain elongation and viral RNA-dependent RNA polymerase activity. This blocks HCV RNA production, thereby inhibiting viral replication.
Valopicitabine HCl is also known as NM283 dihydrochloride. It is a nucleoside analog and the orally bioavailable prodrug of the potent anti-HCV agent 2'-C-methylcytidine (NM107). It was developed for the treatment of chronic hepatitis C but its development was discontinued. This product is for research use only. |
| Molecular Formula |
C15H26CL2N4O6
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|---|---|
| Molecular Weight |
429.296142101288
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| Exact Mass |
428.123
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| CAS # |
640725-71-9
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| Related CAS # |
Valopicitabine;640281-90-9
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| PubChem CID |
11293303
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| Appearance |
White to off-white solid powder
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| LogP |
1.008
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
607
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC(C)[C@@H](C(=O)O[C@@H]1[C@H](O[C@H]([C@]1(C)O)N2C=CC(=NC2=O)N)CO)N.Cl.Cl
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| InChi Key |
XENHXZMAOSTXGD-DSMKLBDQSA-N
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| InChi Code |
InChI=1S/C15H24N4O6.2ClH/c1-7(2)10(17)12(21)25-11-8(6-20)24-13(15(11,3)23)19-5-4-9(16)18-14(19)22;;/h4-5,7-8,10-11,13,20,23H,6,17H2,1-3H3,(H2,16,18,22);2*1H/t8-,10+,11-,13-,15-;;/m1../s1
|
| Chemical Name |
[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] (2S)-2-amino-3-methylbutanoate;dihydrochloride
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
H2O : ~100 mg/mL (~232.94 mM)
DMSO : ~100 mg/mL (~232.94 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 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 (5.82 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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3294 mL | 11.6469 mL | 23.2937 mL | |
| 5 mM | 0.4659 mL | 2.3294 mL | 4.6587 mL | |
| 10 mM | 0.2329 mL | 1.1647 mL | 2.3294 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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