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Purity: ≥98%
PSI-6206 13CD3 (RO-2433 13CD3; GS-331007 13CD3; Sofosbuvir metabolite GS-331007 13CD3) is the deuterium labeled form of PSI-6206. PSI-6206 is the deaminated derivative of PSI-6130, which is a potent and selective inhibitor of HCV NS5B polymerase. PSI-6206 inhibits HCV replicon with EC90 of >100 μM. Sofosbuvir (also known as PSI-7977, GS-7977; trade names Sovaldi and Virunon) is a HCV NS5B polymerase inhibitor that is used for the treatment of chronic hepatitis C virus (HCV) infection. Sofosbuvir acts by inhibiting the RNA polymerase that the hepatitis C virus uses to replicate its RNA. It is a component of the first all-oral, interferon-free regimen approved for treating chronic Hepatitis C. In 2013, the FDA approved sofosbuvir in combination with ribavirin (RBV) for oral dual therapy of HCV genotypes 2 and 3, and for triple therapy with injected pegylated interferon (pegIFN) and RBV for treatment-naive patients with HCV genotypes 1 and 4.
PSI-6206 13CD3 (CAS: 1256490-42-2) is the stable isotope-labeled version of the non-cytosine uridine metabolite PSI-6206, featuring a carbon-13 (¹³C) and three deuterium (²H or D) atoms on the methyl group at the 2'-position of the ribose ring. With a molecular formula of C₉(¹³C)H₁₀D₃FN₂O₅ and a molecular weight of 264.23 g/mol, this isotopologue is chemically identical to the non-labeled compound but heavier, making it an ideal internal standard for quantitative analysis in mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. The compound is a white to light yellow solid powder, soluble in DMSO (10 mM), and should be stored at -20°C for long-term stability.| Targets |
PSI-6206 13CD3 is the labeled analog of PSI-6206, the deaminated derivative of the potent and selective HCV NS5B polymerase inhibitor PSI-6130. The pharmacologically active entity is its intracellular 5'-triphosphate metabolite (RO2433-TP), which targets the HCV NS5B RNA-dependent RNA polymerase (RdRp), acting as a competitive inhibitor of native RNA synthesis with an inhibition constant (Ki) of 0.141 μM.
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| ln Vitro |
As an isotopically labeled compound, PSI-6206 13CD3 is not typically used to measure direct in vitro activity. The activity profile is derived from its non-labeled counterpart, PSI-6206. PSI-6206 itself exhibits low potency against the HCV replicon with an EC₉₀ > 100 μM. Its antiviral activity is dependent on intracellular conversion to the 5'-triphosphate metabolite (RO2433-TP), which inhibits RNA synthesis by the native HCV replicase (IC₅₀ = 1.19 μM) and the recombinant NS5B polymerase (IC₅₀ = 0.52 μM).
As HCV NS5B polymerase inhibitor, PSI-7977 displays more potent inhibitory activity against HCV RNA replication than PSI-7976 with EC50 of 92 nM versus 1.07 μM and EC90 of 0.29 μM versus 2.99 μM, consistent with that incubating clone A cells with PSI-7977 leads to a higher concentration of PSI-7409 than clone A cells incubated with PSI-7976. PSI-7977 is an effective substrate for CatA to form PSI-352707 with 18-30 fold more potency as compared with PSI-7976. Unlike GS-7976, however, the CES1-mediated hydrolysis of PSI-7977 does not progress in a time-dependent manner. The S282T NS5B polymerase mutation but not S96T mutation confers resistance to PSI-7977 with EC90 increases from 0.42 μM to 7.8 μM. When assessed in an 8-day cytotoxicity assay, PSI-7977 displays no cytotoxicity against Huh7, HepG2, BxPC3, and CEM cells even at concentrations up to 100 μM. PSI-7977 treatment for 14 days shows a IC90 of 72.1 μM and 68.6 μM for the inhibition of mtDNA and rDNA, respectively, in HepG2 cells. PSI-7977 exhibits potent activity against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Sequence analysis of the JFH-1 NS5B region indicates that additional amino acid changes including T179A, M289L, I293L, M434T, and H479P are selected both prior to and after the emergence of S282T, which are required to confer resistance to PSI-7977. |
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| ln Vivo |
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| Enzyme Assay |
For its non-labeled counterpart, the active 5'-triphosphate metabolite (RO2433-TP) was evaluated for inhibition of RNA synthesis. The assay used purified recombinant HCV Con1 NS5B polymerase and a heteropolymeric RNA template derived from the 3'-end of the negative strand of the HCV genome. The reaction mixture, containing the polymerase, RNA template, ribonucleoside triphosphates (including a radiolabeled tracer), and varying concentrations of the inhibitor, was incubated. The IC₅₀ (0.52 μM) and Ki (0.141 μM) values were determined by measuring the amount of radiolabel incorporated into newly synthesized RNA.
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| Cell Assay |
Cells (Huh7, HepG2, BxPC3, and CEM) are exposed to various concentrations of PSI-7977 for 8 days. At the end of the growth period, MTS dye from the CellTiter 96 AQueous One Solution Cell Proliferation Assay kit is added to each well, and the plate is incubated for an additional 2 hours. The absorbance at 490 nm is read with a Victor3 plate reader using themedium only controlwells as blanks. The 50% inhibition value (IC50) is determined by comparing the absorbance in wells containing cells and PSI-7977 to untreated cell control wells.
For its non-labeled counterpart, the HCV subgenomic replicon assay is used. Huh-7 or other hepatoma cells harboring HCV replicons are treated with serial dilutions of the compound. After a 3-day incubation, total RNA is extracted, and HCV RNA levels are quantified by real-time RT-PCR. The EC₉₀ of PSI-6206 was determined to be >100 μM, confirming its lack of direct antiviral activity prior to intracellular phosphorylation. |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
PSI-6206 13CD3 is used as an internal standard to accurately measure the levels of PSI-6206 in biological matrices by LC-MS/MS. In rhesus monkeys, following oral administration of PSI-6130 (33.3 mg/kg), the total oral bioavailability of PSI-6130 plus its deaminated metabolite PSI-6206 was 64% ± 26%. The majority of drug recovered in urine was in the form of PSI-6206. In human clinical studies of Sofosbuvir, PSI-6206 (GS-331007) is the predominant circulating nucleoside metabolite, with a terminal elimination half-life (t₁/₂) ranging from 25.7 to 32.7 hours in healthy volunteers.
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| Toxicity/Toxicokinetics |
As a stable isotope-labeled compound intended for use as a research standard, it is considered non-hazardous when handled with standard laboratory precautions. PSI-6206, the unlabeled compound, has shown low cytotoxicity in vitro, with no significant effects observed in Huh7, HepG2, BxPC3, and CEM cells at concentrations up to 100 μM. The compound is for research use only and not for human or veterinary use
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| Additional Infomation |
PSI-6206 13CD3 is a crucial tool for pharmaceutical research, enabling precise quantification of drug metabolites in complex biological samples. Synonyms include RO-2433 13CD3, GS-331007 13CD3, and Sofosbuvir metabolite GS-331007 13CD3. The labeled methyl group (¹³CD₃) is located at the 2' position of the ribose ring, which is the site of the 2'-C-methyl modification critical for the compound's mechanism of action as a non-obligate chain terminator when phosphorylated to its triphosphate form.
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| Molecular Formula |
C913CH10D3FN2O5
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| Molecular Weight |
264.23
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| Exact Mass |
264.103
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| CAS # |
1256490-42-2
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| Related CAS # |
PSI-6206;863329-66-2
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| PubChem CID |
58463518
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| Appearance |
White to light yellow solid powder
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| LogP |
-1.1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
415
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[2H][13C]([2H])([2H])[C@]1([C@@H]([C@H](O[C@H]1N2C=CC(=O)NC2=O)CO)O)F
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| InChi Key |
ARKKGZQTGXJVKW-CWDGLZGLSA-N
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| InChi Code |
InChI=1S/C10H13FN2O5/c1-10(11)7(16)5(4-14)18-8(10)13-3-2-6(15)12-9(13)17/h2-3,5,7-8,14,16H,4H2,1H3,(H,12,15,17)/t5-,7-,8-,10-/m1/s1/i1+1D3
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| Chemical Name |
1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-(trideuterio(113C)methyl)oxolan-2-yl]pyrimidine-2,4-dione
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| Synonyms |
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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 |
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| 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 (378.5 mM)
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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 | 3.7846 mL | 18.9229 mL | 37.8458 mL | |
| 5 mM | 0.7569 mL | 3.7846 mL | 7.5692 mL | |
| 10 mM | 0.3785 mL | 1.8923 mL | 3.7846 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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