![L-Alanine, N-[(S)-(4-nitrophenoxy)phenoxyphosphinyl]-, 1-methylethyl ester](/upload/1124/V68067.png)
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| 10mg |
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| Targets |
The molecular target is the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication. As a phosphoramidate prodrug intermediate, this compound undergoes metabolic activation to the pharmacologically active uridine analog triphosphate, which acts as a chain terminator and competitive inhibitor of NS5B polymerase, thereby blocking HCV RNA synthesis.
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| ln Vitro |
Commercial ergot supplements have been made from amino acids and their derivatives. They affect the release of anabolic hormones, the availability of fuel for activity, the ability to think clearly under pressure, and the prevention of muscular damage brought on by exertion. They are regarded as advantageous synergistic food ingredients [1].
This compound serves as an intermediate in Sofosbuvir synthesis rather than a directly active molecule. The parent drug Sofosbuvir shows potent in vitro activity against HCV genotypes 1-6, with EC50 values in the low nanomolar range (0.4-1.4 nM) in replicon assays. The active triphosphate metabolite inhibits NS5B polymerase with Ki values around 0.02-0.04 uM. |
| ln Vivo |
The parent drug Sofosbuvir is highly effective in vivo, achieving sustained virologic response (SVR) rates of 90-100% in clinical trials for HCV patients. Following oral administration, Sofosbuvir is rapidly absorbed and converted to the active triphosphate in hepatocytes. The compound has transformed hepatitis C therapy, reducing treatment duration to 8-12 weeks with minimal side effects.
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| Enzyme Assay |
Cell-free NS5B polymerase assays are performed using purified HCV NS5B enzyme, RNA template/primer, nucleotides including alpha-32P-labeled UTP, and varying concentrations of the active triphosphate metabolite. Reactions are incubated at 30degC for 60-120 minutes, then products resolved by gel electrophoresis or captured on filters for scintillation counting to determine IC50/Ki.
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| Cell Assay |
Cell-based replicon assays for Sofosbuvir use Huh-7 hepatoma cells stably expressing HCV subgenomic replicon with luciferase or neomycin resistance reporter. Cells are treated with compound (0.01-10 uM) for 48-72 hours, then luciferase activity measured or colony formation assessed after G418 selection to determine EC50 for viral replication inhibition.
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| Animal Protocol |
Animal studies for Sofosbuvir are conducted in chimeric mice with humanized livers or in HCV-infected non-human primates. Animals receive oral gavage of parent drug (10-100 mg/kg). Endpoints include plasma HCV RNA levels by qRT-PCR, liver compound concentrations by LC-MS/MS, and histopathological assessment of hepatic inflammation and fibrosis.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Sofosbuvir in humans include rapid oral absorption (Tmax ~0.5-1 hour), peak plasma concentration ~500-1500 ng/mL, plasma half-life ~0.5-1 hour for parent drug but longer for active triphosphate in hepatocytes (t1/2 ~20-40 hours), volume of distribution ~25 L, and elimination via renal excretion of inactive metabolite GS-331007.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of Sofosbuvir shows favorable safety profile. Common adverse effects include mild headache, fatigue, nausea, and insomnia (＜20% incidence). Severe adverse effects occur in ＜1% of patients. No clinically significant drug-drug interactions with most antiretrovirals. Cardiotoxicity is minimal with no QT prolongation observed. Hepatotoxicity is rare.
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| References | |
| Additional Infomation |
This compound is a white to off-white solid powder with molecular formula C18H21N2O7P, molecular weight 408.34, and purity ≥98%. It is a synthetic intermediate for Sofosbuvir production and is intended for research and pharmaceutical manufacturing use only. Not for direct human administration.
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| Molecular Formula |
C18H21N2O7P
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| Molecular Weight |
408.34
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| Exact Mass |
408.109
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| CAS # |
1256490-31-9
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| PubChem CID |
56648977
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| Appearance |
White to off-white solid powder
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| LogP |
5.004
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
28
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| Complexity |
567
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC1=CC=CC=C1)OC2=CC=C(C=C2)[N+](=O)[O-]
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| InChi Key |
NYJKISSOEZMRHH-POXGOYDTSA-N
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| InChi Code |
InChI=1S/C18H21N2O7P/c1-13(2)25-18(21)14(3)19-28(24,26-16-7-5-4-6-8-16)27-17-11-9-15(10-12-17)20(22)23/h4-14H,1-3H3,(H,19,24)/t14-,28-/m0/s1
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| Chemical Name |
propan-2-yl (2S)-2-[[(4-nitrophenoxy)-phenoxyphosphoryl]amino]propanoate
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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: 100 mg/mL (244.89 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 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 (6.12 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 (6.12 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 | 2.4489 mL | 12.2447 mL | 24.4894 mL | |
| 5 mM | 0.4898 mL | 2.4489 mL | 4.8979 mL | |
| 10 mM | 0.2449 mL | 1.2245 mL | 2.4489 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.
Products are for research use only; We do not sell to patients
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