| Size | Price | Stock | Qty |
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| 100mg |
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| Targets |
The primary target of valopicitabine is the HCV NS5B RNA-dependent RNA polymerase, an essential enzyme for viral replication. After oral administration, valopicitabine is converted to 2'-C-methylcytidine (NM107) primarily through hydrolysis of the valine ester. NM107 is then phosphorylated intracellularly to its 5'-triphosphate form, which competitively inhibits NS5B polymerase, causing chain termination and blocking viral RNA chain elongation. This mechanism disrupts HCV RNA production and inhibits viral replication.
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| ln Vitro |
In vitro, valopicitabine itself is a prodrug with minimal direct activity until converted to NM107. NM107, the active metabolite, competitively inhibits NS5B polymerase and causes chain termination. The compound has potent antiviral activity against HCV. NM107 inhibits HCV replication in cell-based replicon assays with EC₅0 values in the low micromolar range. The compound's mechanism as a nucleoside analog that gets incorporated into nascent viral RNA and terminates chain elongation is similar to other nucleoside HCV inhibitors.
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| ln Vivo |
In Sprague-Dawley rats, valopitabine (NM283) (100 mg/kg; oral) showed Cmax, AUC, t1/2, and tmax values of 3.624 μg/mL, 8.95 μg h/mL, 0.64 hours, and 1 hour, correspondingly. 2].
In vivo, valopicitabine demonstrates potent antiviral activity against chronic hepatitis C virus genotype-1 in chimpanzees. The compound is orally bioavailable, allowing convenient oral dosing. In Sprague-Dawley rats, valopicitabine (100 mg/kg; oral) shows Cmax of 3.624 microg/mL, AUC of 8.95 microg·h/mL, terminal elimination half-life (t1/2) of 0.64 hours, and tmax of 1 hour. The rapid conversion to NM107 in vivo provides sustained antiviral activity. Although clinical development was discontinued, valopicitabine was evaluated in Phase II clinical trials for chronic hepatitis C. |
| Enzyme Assay |
For NS5B polymerase inhibition assays, use recombinant HCV NS5B polymerase (genotype 1b, delta21). Incubate enzyme (50-100 nM) with 1 uM poly(A)/oligo(U) template-primer or HCV RNA template, varying concentrations of valopicitabine or NM107 triphosphate (0.001-100 uM), 1 uM [3H]-UTP, and assay buffer (50 mM HEPES pH 7.5, 5 mM MgCl2, 10 mM KCl, 1 mM DTT, 0.1% Triton X-100). Incubate at 30degC for 30-60 min. Terminate by spotting onto DE81 filter papers or adding 10% TCA, wash, and measure incorporated radioactivity by scintillation counting. Calculate IC₅0 from dose-response curves.
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| Cell Assay |
For HCV replicon assays, use Huh-7 cells stably expressing HCV replicon RNA. Culture in DMEM with 10% FBS and G418 (0.5-1 mg/mL) at 37degC with 5% CO2. Treat cells with valopicitabine or NM107 (0.01-100 uM) for 72 h. Isolate total RNA, perform qRT-PCR for HCV RNA (5'UTR region), and normalize to GAPDH or beta-actin. Calculate EC₅0 and EC₉0 values. Assess cell viability using MTT or CellTiter-Glo to ensure cytotoxicity does not contribute to antiviral effects.
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| Animal Protocol |
For in vivo pharmacokinetic and antiviral studies, use male Sprague-Dawley rats (200-250 g) or HCV-infected chimpanzees. For rat PK studies, administer valopicitabine as a single oral dose of 100 mg/kg in 0.5% methylcellulose or 10% DMSO/90% corn oil. Collect blood at multiple time points (0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 h post-dose) via tail vein or cardiac puncture. Plasma samples are analyzed by LC-MS/MS to measure valopicitabine and NM107 concentrations. Calculate PK parameters (Cmax, Tmax, AUC, t1/2, clearance, volume of distribution) using non-compartmental analysis. For antiviral efficacy in chimpanzees (HCV genotype 1-infected, 40-60 kg), administer valopicitabine orally at 10-30 mg/kg twice daily for 4-12 weeks. Monitor plasma HCV RNA levels by RT-PCR weekly. Assess safety through clinical observations, body weight, serum chemistry, hematology, and liver histology. For mice models, a humanized liver chimeric mouse (e.g., uPA/SCID, FRG) infected with HCV can be used; administer valopicitabine orally at 50-200 mg/kg daily for 2-4 weeks. Collect blood weekly for viral RNA quantification and sacrifice at study endpoint for liver HCV RNA measurement.
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| ADME/Pharmacokinetics |
Valopicitabine has a molecular formula C1₅H24N4O₆ and molecular weight 356.37 g/mol. It is the 3-O-valine ester prodrug of 2'-C-methylcytidine (NM107). In Sprague-Dawley rats, oral administration of 100 mg/kg valopicitabine yields a Cmax of 3.624 microg/mL, AUC of 8.95 microg·h/mL, and terminal half-life of 0.64 hours, with Tmax of 1 hour. The compound is rapidly converted to NM107 in vivo. Solubility information: soluble in DMSO for in vitro use. For in vivo oral dosing, can be suspended in 0.5% methylcellulose or formulated in 10% DMSO/90% corn oil. Storage: powder at -20degC for up to 3 years, 4degC for 2 years; in solvent at -80degC for 6 months, -20degC for 1 month.
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| Toxicity/Toxicokinetics |
Based on clinical trial data, valopicitabine was generally well-tolerated but development was discontinued due to gastrointestinal side effects (nausea, diarrhea) and limited efficacy. For research use, standard precautions apply: use personal protective equipment (gloves, lab coat), avoid inhalation, ingestion, and skin contact. The compound is for research use only and not for human use. No specific teratogenicity or carcinogenicity data are available for research-grade product. Consult the safety data sheet before handling. Dispose of waste in accordance with local regulations for chemical and biological waste. Although clinical development has been discontinued, the compound remains a useful research tool for studying HCV replication and nucleoside analog mechanisms.
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| References |
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| Additional Infomation |
Valopicitabine is a 3-O-valine ester prodrug of the nucleoside analog 2'-C-methylcytidine, possessing 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 the production of HCV RNA, thereby inhibiting viral replication. [From the National Cancer Institute, USA]
Valopicitabine (NM283) was developed by Idenix Pharmaceuticals as an oral prodrug for the treatment of chronic hepatitis C (HCV). Its active metabolite, NM107, is a 2'-C-methylcytidine nucleoside analog that competitively inhibits HCV NS5B RNA-dependent RNA polymerase. After valopicitabine is absorbed, it is converted to NM107, which is then phosphorylated to its 5'-triphosphate form, incorporating into nascent viral RNA and causing premature chain termination, thus blocking HCV RNA replication. Valopicitabine entered clinical trials (Phase II) but development was discontinued due to gastrointestinal side effects and modest efficacy compared to emerging direct-acting antivirals. It remains a valuable research tool for studying HCV replication mechanisms, nucleoside analog pharmacology, and prodrug strategies. It is not FDA-approved for clinical use. |
| Molecular Formula |
C15H24N4O6
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|---|---|
| Molecular Weight |
356.37426
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| Exact Mass |
356.17
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| CAS # |
640281-90-9
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| Related CAS # |
Valopicitabine dihydrochloride;640725-71-9
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| PubChem CID |
6918726
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
-2
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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 |
6
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| Heavy Atom Count |
25
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| Complexity |
607
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| Defined Atom Stereocenter Count |
5
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| SMILES |
CC(C)C(C(=O)OC1C(OC(C1(C)O)N2C=CC(=NC2=O)N)CO)N
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| InChi Key |
TVRCRTJYMVTEFS-ICGCPXGVSA-N
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| InChi Code |
InChI=1S/C15H24N4O6/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)/t8-,10+,11-,13-,15-/m1/s1
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| 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
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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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8061 mL | 14.0304 mL | 28.0607 mL | |
| 5 mM | 0.5612 mL | 2.8061 mL | 5.6121 mL | |
| 10 mM | 0.2806 mL | 1.4030 mL | 2.8061 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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