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Antimicrobial Agents and Chemotherapy, June 1998, p. 1340-1345, Vol. 42, No. 6
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.
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

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