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Chemical Compound Review:

SureCN465678 4-amino-1-[2-(hydroxymethyl)- 1,3...

Synonyms: AG-D-70884, ACMC-209tyk, ACMC-20mvgi, NSC-620753, NSC-760061, ...

Boucher, C.A. et al., Johnson, M.A. et al., Morrey, J.D. et al., Palmer, S. et al., Gao, Q. et al., et al.

Morrey, Bailey, Korba, Sidwell,

Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of BCH-189

Development of HIV-1 resistance to (-)2'-deoxy-3'-thiacytidine in patients with AIDS or advanced AIDS-related complex [1].
Lamivudine (3TC), the negative enantiomer of 2'-deoxy-3'-thiacytidine, is a dideoxynucleoside analogue used in combination with other agents in the treatment of human immunodeficiency virus type 1 (HIV-1) infection and as monotherapy in the treatment of hepatitis B virus (HBV) infection [2].
The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1 [3].
Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog [4].
Cytidine deaminase from Escherichia coli is shown here to deaminate 2'-deoxy-3'-thiacytidine enantioselectively to leave 3TC essentially optically pure [5].

High impact information on BCH-189

Clinical isolates of HIV-1 which are (-) 2'-deoxy-3'-thiacytidine-resistant also displayed resistance to both (+)dOTFC and (-)dOTFC [6].
The M539V polymerase variant of human hepatitis B virus demonstrates resistance to 2'-deoxy-3'-thiacytidine and a reduced ability to synthesize viral DNA [7].
The intracellular phosphorylation of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine was increased two- to threefold by the addition of hydroxyurea (HU) to the single drugs or to the two drugs in combination [8].
Passage of human immunodeficiency virus type 1 in the presence of increasing 2'-deoxy-3'-thiacytidine (3TC) concentrations results in high-level (> 100-fold) 3TC-resistant viruses [9].
High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase [9].

Chemical compound and disease context of BCH-189

Lamivudine ([-]2'-deoxy-3'-thiacytidine), known to reduce hepatitis B viremia in human patients, and zidovudine (3'-azido-3'-deoxythymidine), previously shown to be ineffective for HBV infections in man, were used in parallel in this transgenic animal model [10].

Associations of BCH-189 with other chemical compounds

Determination of 2'-deoxy-3'-thiacytidine (3TC) in human urine by liquid chromatography: direct injection with column switching [11].

References

Development of HIV-1 resistance to (-)2'-deoxy-3'-thiacytidine in patients with AIDS or advanced AIDS-related complex. Wainberg, M.A., Salomon, H., Gu, Z., Montaner, J.S., Cooley, T.P., McCaffrey, R., Ruedy, J., Hirst, H.M., Cammack, N., Cameron, J. AIDS (1995) [Pubmed]
Clinical pharmacokinetics of lamivudine. Johnson, M.A., Moore, K.H., Yuen, G.J., Bye, A., Pakes, G.E. Clinical pharmacokinetics. (1999) [Pubmed]
The same mutation that encodes low-level human immunodeficiency virus type 1 resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine confers high-level resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine. Gao, Q., Gu, Z., Parniak, M.A., Cameron, J., Cammack, N., Boucher, C., Wainberg, M.A. Antimicrob. Agents Chemother. (1993) [Pubmed]
Anti-human immunodeficiency virus type 1 activity and in vitro toxicity of 2'-deoxy-3'-thiacytidine (BCH-189), a novel heterocyclic nucleoside analog. Soudeyns, H., Yao, X.I., Gao, Q., Belleau, B., Kraus, J.L., Nguyen-Ba, N., Spira, B., Wainberg, M.A. Antimicrob. Agents Chemother. (1991) [Pubmed]
Enzymatic production of optically pure (2'R-cis)-2'-deoxy-3'-thiacytidine (3TC, lamivudine): a potent anti-HIV agent. Mahmoudian, M., Baines, B.S., Drake, C.S., Hale, R.S., Jones, P., Piercey, J.E., Montgomery, D.S., Purvis, I.J., Storer, R., Dawson, M.J. Enzyme Microb. Technol. (1993) [Pubmed]
Selection and characterization of human immunodeficiency virus type 1 variants resistant to the (+) and (-) enantiomers of 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine. Richard, N., Salomon, H., Rando, R., Mansour, T., Bowlin, T.L., Wainberg, M.A. Antimicrob. Agents Chemother. (2000) [Pubmed]
The M539V polymerase variant of human hepatitis B virus demonstrates resistance to 2'-deoxy-3'-thiacytidine and a reduced ability to synthesize viral DNA. Ladner, S.K., Miller, T.J., King, R.W. Antimicrob. Agents Chemother. (1998) [Pubmed]
Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of hydroxyurea. Palmer, S., Cox, S. Antimicrob. Agents Chemother. (1997) [Pubmed]
High-level resistance to (-) enantiomeric 2'-deoxy-3'-thiacytidine in vitro is due to one amino acid substitution in the catalytic site of human immunodeficiency virus type 1 reverse transcriptase. Boucher, C.A., Cammack, N., Schipper, P., Schuurman, R., Rouse, P., Wainberg, M.A., Cameron, J.M. Antimicrob. Agents Chemother. (1993) [Pubmed]
Utilization of transgenic mice replicating high levels of hepatitis B virus for antiviral evaluation of lamivudine. Morrey, J.D., Bailey, K.W., Korba, B.E., Sidwell, R.W. Antiviral Res. (1999) [Pubmed]
Determination of 2'-deoxy-3'-thiacytidine (3TC) in human urine by liquid chromatography: direct injection with column switching. Morris, D.M., Selinger, K. Journal of pharmaceutical and biomedical analysis. (1994) [Pubmed]

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