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NHC-triphosphate-tetraammonium
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| Category | Hepatitis C Virus (HCV) |
| Description | NHC-triphosphate tetraammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC)(HY-125033) as a triphosphate form. NHC-triphosphate tetraammonium is a weak alternative substrate for the viralpolymerase and can be incorporated into HCV replicon RNA. |
Product Information
| Molecular Weight | 567.28 |
| Molecular Formula | C9H28N7O15P3 |
| Purity | ≥98% (HPLC) |
| Solubility | In vitro: 10 mM in DMSO |
| Appearance | White to off-white (Solid) |
| Storage | -80°C, protect from light, stored under nitrogen |
| In Vitro | In an intracellular metabolism assay, HCV replicon cells are treated with 10 μM 3H-labeled NHC, and intracellular nucleotide levels are determined after 1, 2 and 8 hours incubations. NHC is rapidly convered into the mono-, di-, and triphosphate forms, and NHC-TP reaches up to 71.12 pM after 8 hours. NHC-triphosphate tetraammonium (NHC-TP) (5-40 μM) absence leads to full-length polymerization products, it can be a weak alternative substrate. In addition, incorporation of NHC-TP instead of CTP increases the molecular weight of the polymerization product by 16 (one extra oxygen) for each event and an obvious electrophoretic shift is observed in cell-free HCV NS5B polymerization reactions Huh-7 cells are incubated with (10-50 μM; 4 h) NHC or a McGuigan phosphoramidate prodrug of NHC. Intracellular levels of the parental compounds and phosphorylated metabolites are measured using LC-MS/MS. Small amounts of NHC- monophosphate (MP) and NHC-diphosphate (DP) can be observed, while NHC-triphosphate tetraammonium (HY-135867) remains the most abundant metabolite. NHC-triphosphate tetraammonium (NHC-TP) metabolite may directly target the viral polymerase and behave as a nonobligate chain terminator. It plays a prominent role in inhibiting early negative-strand RNA synthesis, either through chain termination or mutagenesis, which may in turn interfere with correct replicase complex formation. |
| PSA | 306.09000 |
| Target | IC50: alternative substrate for the viral polymerase |
