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CAS No. : 34973-27-8

MCE 国际站：NHC-triphosphate

产品活性：NHC-triphosphate 是 NHC (HY-125033) 的活性胞内磷酸盐代谢物 (intracellular metabolite )，以三磷酸盐的形式存在。NHC-triphosphate 是病毒聚合酶 (viral polymerase) 的弱底物替代物，会被并入 HCV 复制子 RNA 中。

研究领域：Metabolic Enzyme/Protease  |  Anti-infection  |  Cell Cycle/DNA Damage

作用靶点：Endogenous Metabolite  |  Enterovirus  |  HCV  |  Topoisomerase  |  SARS-CoV

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.

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