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CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity.
Antimicrob Agents Chemother. 2009 Jan; 53(1):186-92.AA

Abstract

Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for the treatment of and prophylaxis against influenza. In this paper, the new potent NA inhibitor R-125489 is reported for the first time. R-125489 inhibited the NA activities of various type A and B influenza viruses, including subtypes N1 to N9 and oseltamivir-resistant viruses. The survival effect of R-125489 was shown to be similar to that of zanamivir when administered intranasally in a mouse influenza virus A/Puerto Rico/8/34 infection model. Moreover, we found that the esterified form of R-125489 showed improved efficacy compared to R-125489 and zanamivir, depending on the acyl chain length, and that 3-(O)-octanoyl R-125489 (CS-8958) was the best compound in terms of its life-prolonging effect (P < 0.0001, compared to zanamivir) in the same infection model. A prolonged survival effect was observed after a single administration of CS-8958, even if it was given 7 days before infection. It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor and shows in vivo efficacy as a result of a single intranasal administration.

Authors+Show Affiliations

Biological Research Laboratories IV, Daiichi Sankyo Co Ltd, Hiromachi, Shinagawa, Tokyo, Japan. yamashita.makoto.yr@daiichisankyo.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18955520

Citation

Yamashita, Makoto, et al. "CS-8958, a Prodrug of the New Neuraminidase Inhibitor R-125489, Shows Long-acting Anti-influenza Virus Activity." Antimicrobial Agents and Chemotherapy, vol. 53, no. 1, 2009, pp. 186-92.
Yamashita M, Tomozawa T, Kakuta M, et al. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother. 2009;53(1):186-92.
Yamashita, M., Tomozawa, T., Kakuta, M., Tokumitsu, A., Nasu, H., & Kubo, S. (2009). CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrobial Agents and Chemotherapy, 53(1), 186-92. https://doi.org/10.1128/AAC.00333-08
Yamashita M, et al. CS-8958, a Prodrug of the New Neuraminidase Inhibitor R-125489, Shows Long-acting Anti-influenza Virus Activity. Antimicrob Agents Chemother. 2009;53(1):186-92. PubMed PMID: 18955520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. AU - Yamashita,Makoto, AU - Tomozawa,Takanori, AU - Kakuta,Masayo, AU - Tokumitsu,Akane, AU - Nasu,Hatsumi, AU - Kubo,Shuku, Y1 - 2008/10/27/ PY - 2008/10/29/pubmed PY - 2009/4/21/medline PY - 2008/10/29/entrez SP - 186 EP - 92 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 53 IS - 1 N2 - Two neuraminidase (NA) inhibitors, zanamivir (Relenza) and oseltamivir phosphate (Tamiflu), have been licensed for the treatment of and prophylaxis against influenza. In this paper, the new potent NA inhibitor R-125489 is reported for the first time. R-125489 inhibited the NA activities of various type A and B influenza viruses, including subtypes N1 to N9 and oseltamivir-resistant viruses. The survival effect of R-125489 was shown to be similar to that of zanamivir when administered intranasally in a mouse influenza virus A/Puerto Rico/8/34 infection model. Moreover, we found that the esterified form of R-125489 showed improved efficacy compared to R-125489 and zanamivir, depending on the acyl chain length, and that 3-(O)-octanoyl R-125489 (CS-8958) was the best compound in terms of its life-prolonging effect (P < 0.0001, compared to zanamivir) in the same infection model. A prolonged survival effect was observed after a single administration of CS-8958, even if it was given 7 days before infection. It is suggested that intranasally administered CS-8958 works as a long-acting NA inhibitor and shows in vivo efficacy as a result of a single intranasal administration. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/18955520/CS_8958_a_prodrug_of_the_new_neuraminidase_inhibitor_R_125489_shows_long_acting_anti_influenza_virus_activity_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=18955520 DB - PRIME DP - Unbound Medicine ER -