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Chemical Compound Review:

Amitivir 1,3,4-thiadiazol-2-ylcyanamide

Synonyms: CHEMBL2104066, AC1Q4SND, CTK8G5737, LY-217896, AKOS006271737, ...

Colacino, J.M. et al., Hayden, F.G. et al., Herman, J.L. et al., Ehlhardt, W.J. et al., Bonate, P.L. et al.

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Disease relevance of Amitivir

Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans [1].
In the ferret, LY217896 was effective in preventing fever induced by influenza virus [2].
1,3,4-Thiadiazol-2-ylcyanamide (LY217896) and its sodium salt were shown to be effective against influenza A and B viruses in vitro and in the mouse model [2].
The efficacy and safety of oral LY217896 for prevention of experimental influenza A/Kawasaki/86 (H1N1) virus infection were assessed in susceptible males randomly assigned to receive LY217896 (75 mg) or placebo once daily for 7 days beginning 24 h prior to viral challenge [1].
In nondividing confluent MDCK cells, the 50% inhibitory concentration of LY217896 ranged from 0.37 to 1.19 micrograms/ml against various strains of influenza A virus and from 0.75 to 1.54 micrograms/ml against various strains of influenza B virus, with no apparent cytotoxicity [2].

High impact information on Amitivir

The rates of virus shedding (100% in both groups), days of viral shedding (3.1 +/- 1.3 for the LY217896 group; 2.8 +/- 1.3 for the placebo group), and titers of virus in nasal washings did not differ between the groups [1].
Administration of LY217896 to uninfected mice did not induce interferon-like activity or interfere with natural killer cell function [2].
The biotransformation of the antiinfluenza agent 1,3,4-thiadiazol-2-ylcyanamide (LY217896, I) was studied [3].
Antiviral compound LY217896 sodium demonstrated developmental toxicity in the pregnant NZW rabbit following multiple oral doses of 10 mg/kg on gestation days 6 through 18 [4].
Uptake and biodisposition of 2-ylcyanamide-1,3,4-thiadiazole (LY217896) by red blood cells [5].

Analytical, diagnostic and therapeutic context of Amitivir

LY217896 (9 mg/m2 of body surface area per day) administered in the diet, in the drinking water, by oral gavage, by intraperitoneal injection, or by aerosolization was well tolerated and protected CD-1 mice infected with a lethal dose of influenza A or B virus [2].

References

Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans. Hayden, F.G., Tunkel, A.R., Treanor, J.J., Betts, R.F., Allerheiligen, S., Harris, J. Antimicrob. Agents Chemother. (1994) [Pubmed]
Evaluation of the anti-influenza virus activities of 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and its sodium salt. Colacino, J.M., DeLong, D.C., Nelson, J.R., Spitzer, W.A., Tang, J., Victor, F., Wu, C.Y. Antimicrob. Agents Chemother. (1990) [Pubmed]
Biotransformation of the antiviral agent 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and characteristics of a mesoionic ribose metabolite. Ehlhardt, W.J., Wheeler, W.J., Breau, A.P., Chay, S.H., Birch, G.M. Drug Metab. Dispos. (1993) [Pubmed]
Quantitative whole-body autoradiography in pregnant rabbits to determine fetal exposure of potential teratogenic compounds. Herman, J.L., Chay, S.H. Journal of pharmacological and toxicological methods. (1998) [Pubmed]
Uptake and biodisposition of 2-ylcyanamide-1,3,4-thiadiazole (LY217896) by red blood cells. Bonate, P.L., Peyton, A. Biopharmaceutics & drug disposition. (1995) [Pubmed]

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