NHC-diphosphate triammonium

• CAT Number: I044508
• Molecular Formula: C9H24N6O12P2
• Molecular Weight: 470.27
• Purity: ≥95%
• Synonyms: azane;[(2R,3S,4R,5R)-3,4-dihydroxy-5-[4-(hydroxyamino)-2-oxopyrimidin-1-yl]oxolan-2-yl]methyl phosphono hydrogen phosphate
• InChI: InChI=1S/C9H15N3O12P2.3H3N/c13-6-4(3-22-26(20,21)24-25(17,18)19)23-8(7(6)14)12-2-1-5(11-16)10-9(12)15;;;/h1-2,4,6-8,13-14,16H,3H2,(H,20,21)(H,10,11,15)(H2,17,18,19);3*1H3/t4-,6-,7-,8-;;;/m1.../s1
• InChIKey: IFDLJBUQQGSKTM-LLWADOMFSA-N
• SMILES: C1=CN(C(=O)N=C1NO)C2C(C(C(O2)COP(=O)(O)OP(=O)(O)O)O)O.N.N.N

NHC-diphosphate triammonium is an active phosphorylated intracellular metabolite of β-d-N4-Hydroxycytidine (NHC) (HY-125033) as a diphosphate form[1]. NHC-diphosphate triammonium 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 triammonium (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 triammonium (HY-135867) remains the most abundant metabolite[2].NHC-triphosphate triammonium (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.

Reference

[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.
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[2]. Maryam Ehteshami, et al. Characterization of β-d- N4-Hydroxycytidine as a Novel Inhibitor of Chikungunya Virus.
 [Content Brief]