S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

Abstract

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.

• Authors: T Fujiwara, A Sato, M el-Farrash, S Miki, K Abe, Y Isaka, M Kodama, Y Wu, L B Chen, H Harada, H Sugimoto, M Hatanaka, Y Hinuma
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 42 Issue 6 Pg. 1340-5 (Jun 1998) ISSN: 0066-4804 [Print] United States
• PMID: 9624472 (Publication Type: Journal Article)

Chemical References

• Anti-HIV Agents
• Imidazoles
• S 1153

Topics

• Animals
• Anti-HIV Agents (administration & dosage, pharmacology)
• Cells, Cultured
• Drug Resistance, Microbial
• HIV-1 (drug effects, physiology)
• Humans
• Imidazoles (pharmacology)
• Mice
• Mice, Inbred BALB C
• T-Lymphocytes
• Virus Replication (drug effects)