AAC
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fujiwara, T.
Right arrow Articles by Hinuma, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fujiwara, T.
Right arrow Articles by Hinuma, Y.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 1998, p. 1340-1345, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

S-1153 Inhibits Replication of Known Drug-Resistant Strains of Human Immunodeficiency Virus Type 1

Tamio Fujiwara,1,* Akihiko Sato,1 Mohamed El-Farrash,1,dagger Shigeru Miki,1 Kenji Abe,1 Yoshitaka Isaka,1 Makoto Kodama,1 Yaming Wu,2 Lan Bo Chen,3 Hiroshi Harada,1 Hirohiko Sugimoto,1 Masakazu Hatanaka,1 and Yorio Hinuma1

Shionogi Research Laboratories, Shionogi & Co. Ltd., 5-12-4, Sagisu Fukushima-ku Osaka 553 Japan1; Shionogi BioResearch Corp., Lexington, Massachusetts 021732; and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 021153

Received 2 October 1997/Returned for modification 25 November 1997/Accepted 13 March 1998

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two- to three-drug combination therapy for HIV infection.

* Corresponding author. Mailing address: Shionogi Institute for Medical Science, Shionogi & Co., Ltd., 2-5-1 Mishima, Settsu-shi, 566-0022, Japan. Phone: 81-6-382-2612. Fax: 81-6-382-2598. E-mail: tamio.fujiwara{at}shionogi.co.jp.

dagger Present address: Mansoura University Faculty of Medicine Department of Microbiology and Immunology, Mansoura, Egypt.

Antimicrobial Agents and Chemotherapy, June 1998, p. 1340-1345, Vol. 42, No. 6
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Clin. Vaccine Immunol. Clin. Microbiol. Rev.
J. Clin. Microbiol. ALL ASM JOURNALS

Copyright © 1998 by the American Society for Microbiology. All rights reserved.