NHC-triphosphate tetrasodium
目录号 : GC61961NHC-triphosphate tetrasodium是 NHC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 tetrasodium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。
Sample solution is provided at 25 µL, 10mM.
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NHC-triphosphate tetrasodium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) as a triphosphate form[1]. NHC-triphosphate tetrasodium is a weak alternative substrate for the viral polymerase and can be incorporated into HCV replicon RNA[1][2].
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[1].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[1].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 remains the most abundant metabolite[2].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.
References:
[1]. Stuyver LJ,et al. Ribonucleoside analogue that blocks replication of bovine viral diarrhea and hepatitis C viruses in culture.Antimicrob Agents Chemother. 2003 Jan;47(1):244-54.
[2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.
Cas No. | SDF | ||
Canonical SMILES | O[C@H]1[C@H](N(C=C/C2=N/O)C(N2)=O)O[C@H](COP(OP(OP(O[Na])(O[Na])=O)(O[Na])=O)(O[Na])=O)[C@H]1O | ||
分子式 | C9H12N3Na4O15P3 | 分子量 | 587.08 |
溶解度 | Water : 100 mg/mL (170.33 mM) | 储存条件 | Store at -20°C, sealed storage, away from moisture and light |
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1 mg | 5 mg | 10 mg | |
1 mM | 1.7033 mL | 8.5167 mL | 17.0335 mL |
5 mM | 0.3407 mL | 1.7033 mL | 3.4067 mL |
10 mM | 0.1703 mL | 0.8517 mL | 1.7033 mL |
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