NHC-triphosphate-tetrasodium

Category	Hepatitis C Virus (HCV)
Description	NHC-triphosphate tetrasodium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) (HY-125033) as a triphosphate form. NHC-triphosphate tetrasodium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA.

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Product Information

Molecular Weight	587.08
Molecular Formula	C9H12N3Na4O15P3
Purity	≥98% (HPLC)
Solubility	In vitro: 10 mM in DMSO
Appearance	Solid powder
Storage	Store at -20°C
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 (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 (HY-135867) remains the most abundant metabolite. NHC-triphosphate (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	Endogenous Metabolite; Enterovirus; HCV; Topoisomerase