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Chemical Compound Review:

beta-Fddc 4-amino-5-fluoro-1-[(2S,5R)- 5...

Synonyms: L-FddC, CHEMBL40724, SureCN913431, AG-K-91463, CTK4C5243, ...

Lin, T.S. et al., Zoulim, F. et al., Schinazi, R.F. et al., Gagnon, L. et al., Skalski, V. et al., et al.

Schinazi, Schlueter-Wirtz, Stuyver,

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Disease relevance of beta-Fddc

We evaluated the anti-HBV activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-F-ddC), a beta-L-nucleoside analog derived from 2',3'-dideoxycytidine (ddC), in the duck HBV (DHBV) model [1].
Antiviral activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro [2].
2',3'-Dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC), two nucleosides with "unnatural L-configuration," have been synthesized and found to have potent antiviral activity against hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) in vitro with very little toxicity [2].

High impact information on beta-Fddc

The Ki values of their 5'-triphosphates for DNA polymerase gamma were found to be in the following order: D-ddC < D-FddC L-OddC D-FOddC < L-FOddC << L-FddC [3].
2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo [1].
The monophosphate forms of AZT, D4T, L-FddC and L-ddC were potent inhibitors of the exonuclease at micromolar concentrations, while D-ddCMP partially inhibited the enzyme at millimolar concentrations [4].
All the L-nucleoside analogues tested selected for the V184 mutation, including the L-pyrimidine nucleosides 3TC (-)-FTC, beta- L-FddC, beta-L-D4FC and the beta-L-purine nucleoside. beta-L-D4FC also selected for K/R65 in addition to V184, indicating that these two mutations are linked and compatible in vitro [5].
While demonstrating no obvious morphological toxicity in vivo in mice at concentrations of 75 and 150 mg/kg, 2',3'-dideoxy-beta-L-5-fluorocytidine- treated animals were shown to have considerable increases in CD4/CD8 double positive T lymphocyte population in their blood circulation [6].

Biological context of beta-Fddc

Following oral administration of an equivalent dose, the absolute oral bioavailability of L-FddC derived from L-FddCMP-bisSATE administration was 65% [7].

References

2',3'-dideoxy-beta-L-5-fluorocytidine inhibits duck hepatitis B virus reverse transcription and suppresses viral DNA synthesis in hepatocytes, both in vitro and in vivo. Zoulim, F., Dannaoui, E., Borel, C., Hantz, O., Lin, T.S., Liu, S.H., Trépo, C., Cheng, Y.C. Antimicrob. Agents Chemother. (1996) [Pubmed]
Antiviral activity of 2',3'-dideoxy-beta-L-5-fluorocytidine (beta-L-FddC) and 2',3'-dideoxy-beta-L-cytidine (beta-L-ddC) against hepatitis B virus and human immunodeficiency virus type 1 in vitro. Lin, T.S., Luo, M.Z., Liu, M.C., Pai, S.B., Dutschman, G.E., Cheng, Y.C. Biochem. Pharmacol. (1994) [Pubmed]
L- and D-enantiomers of 2',3'-dideoxycytidine 5'-triphosphate analogs as substrates for human DNA polymerases. Implications for the mechanism of toxicity. Kukhanova, M., Liu, S.H., Mozzherin, D., Lin, T.S., Chu, C.K., Cheng, Y.C. J. Biol. Chem. (1995) [Pubmed]
Removal of anti-human immunodeficiency virus 2',3'-dideoxynucleoside monophosphates from DNA by a novel human cytosolic 3'-->5' exonuclease. Skalski, V., Liu, S.H., Cheng, Y.C. Biochem. Pharmacol. (1995) [Pubmed]
Early detection of mixed mutations selected by antiretroviral agents in HIV-infected primary human lymphocytes. Schinazi, R.F., Schlueter-Wirtz, S., Stuyver, L. Antivir. Chem. Chemother. (2001) [Pubmed]
Immunomodulatory and antiviral activities of 2',3'-dideoxy-beta-L-cytidine and 2',3'-dideoxy-beta-L-5-fluorocytidine. Gagnon, L., Nordstrom, P.A., Duchaine, J., Jutras, D., Hamel, M., Barbeau, D., Hooker, E., Ashman, C., Cammack, N., Tse, A. Immunopharmacology and immunotoxicology. (1995) [Pubmed]
In vitro and in vivo metabolism and pharmacokinetics of bis [(t-butyl)-S-acyl-2-thioethyl]-beta-L-2',3'-dideoxy-5-fluorocytidine monophosphate. Martin, L.T., Cretton-Scott, E., Placidi, L., Faraj, A., Loi, A.G., Schinazi, R.F., McClure, H.M., Gosselin, G., Imbach, J.L., Sommadossi, J.P. Nucleosides Nucleotides Nucleic Acids (2000) [Pubmed]

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