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Chemical Compound Review:

Immusine 3-amino-9-[(2R,3R,4S,5R)-3,4- dihydroxy-5...

Synonyms: Immunosine, Satoribine, Isatoribine, ANA-245, ANA245, ...

Sharma, B.S. et al., Horsmans, Y. et al., Smee, D.F. et al., Smee, D.F. et al., Sharma, B.S. et al., et al.

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Disease relevance of Isatoribine

Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection [1].
These C-nucleosides were evaluated for their ability to provide protection against a lethal Semliki Forest virus infection in mice, relative to 7-thia-8-oxoguanosine which was used as a positive control [2].
We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine [3].
We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T8OG)2 inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3) [4].
Successful immunotherapy of murine melanoma metastases with 7-thia-8-oxoguanosine [5].

High impact information on Isatoribine

In conclusion, systemic administration of the selective TLR7 agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects [1].
A novel immunopotentiating agent, 5-amino-3-beta-D-ribofuranosylthiazolo [4,5-d]pyrimidine-2,7(3H,6H)-dione (7-thia-8-oxoguanosine), lacks virus-inhibitory properties in vitro but induces interferon and potentiates immune functions, such as natural killer cell activity [6].
Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel immunostimulator 7-thia-8-oxoguanosine: increased survival after immunization with vaccine plus 7-thia-8-oxoguanosine [3].
Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for proliferation of T cells [7].

Analytical, diagnostic and therapeutic context of Isatoribine

Interferon induction appears to be the reason for antiviral activity in this model, since up to 10,000 units of interferon/ml were induced in mice 1 h after treatment with 100 mg 7-thia-8-oxoguanosine per kg, and antibody to interferon alpha/beta administered shortly after treatment with the nucleoside negated the antiviral effect [8].

References

Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection. Horsmans, Y., Berg, T., Desager, J.P., Mueller, T., Schott, E., Fletcher, S.P., Steffy, K.R., Bauman, L.A., Kerr, B.M., Averett, D.R. Hepatology (2005) [Pubmed]
Direct C-glycosylation of guanine analogues: the synthesis and antiviral activity of certain 7- and 9-deazaguanine C-nucleosides. Girgis, N.S., Michael, M.A., Smee, D.F., Alaghamandan, H.A., Robins, R.K., Cottam, H.B. J. Med. Chem. (1990) [Pubmed]
Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel immunostimulator 7-thia-8-oxoguanosine: increased survival after immunization with vaccine plus 7-thia-8-oxoguanosine. Sharma, B.S., Balazs, L., Jin, A., Wang, J.C., Jolley, W.B., Robins, R.K. Cancer Immunol. Immunother. (1991) [Pubmed]
Immunomodulatory activity of a novel nucleoside, 7-thia-8-oxoguanosine: I. Activation of natural killer cells in mice. Sharma, B.S., Mhaskar, S., Balazs, L., Siaw, M. Immunopharmacology and immunotoxicology. (1992) [Pubmed]
Successful immunotherapy of murine melanoma metastases with 7-thia-8-oxoguanosine. Sharma, B.S., Balazs, L., Jin, A., Jolley, W.B., Robins, R.K. Clin. Exp. Metastasis (1991) [Pubmed]
Broad-spectrum in vivo antiviral activity of 7-thia-8-oxoguanosine, a novel immunopotentiating agent. Smee, D.F., Alaghamandan, H.A., Cottam, H.B., Sharma, B.S., Jolley, W.B., Robins, R.K. Antimicrob. Agents Chemother. (1989) [Pubmed]
Immunosine (7-thia-8-oxoguanosine) acts as a cofactor for proliferation of T cells. Colić, M., Jandrić, D., Gasić, S., Vucević, D., Popović, P., Medić-Mijacević, L., Rakić, L. Fundamental & clinical pharmacology. (2000) [Pubmed]
Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against Punta Toro virus infections in mice. Smee, D.F., Huffman, J.H., Gessaman, A.C., Huggins, J.W., Sidwell, R.W. Antiviral Res. (1991) [Pubmed]

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