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Arzneimittelforschung 2004; 54(1): 69-77
DOI: 10.1055/s-0031-1296939
Antibiotics · Antiviral Drugs · Chemotherapeutics · Cytostatics
Editio Cantor Verlag Aulendorf (Germany)

In vitro Activity of Stampidine against Primary Clinical Human Immunodeficiency Virus Isolates

Fatih M. Uckun
Drug Discovery Program, Departments of Virology, Bioinformatics, Immunology, and Chemistry, Parker Hughes Cancer Center, St. Paul, MN, USA
,
Sharon Pendergrass
Drug Discovery Program, Departments of Virology, Bioinformatics, Immunology, and Chemistry, Parker Hughes Cancer Center, St. Paul, MN, USA
,
Sanjive Qazi
Drug Discovery Program, Departments of Virology, Bioinformatics, Immunology, and Chemistry, Parker Hughes Cancer Center, St. Paul, MN, USA
,
Taracad K. Venkatachalam
Drug Discovery Program, Departments of Virology, Bioinformatics, Immunology, and Chemistry, Parker Hughes Cancer Center, St. Paul, MN, USA
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Publication History

Publication Date:
25 December 2011 (online)

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Summary

The in vitro activity profile of stampidine (CAS 217178-62-6, STAMP) was examined against clinical isolates of HIV-1. In a side-by-side comparison against 10 zido-vudine-sensitive clinical HIV-1 isolates, STAMP was 100-fold more potent than stavudine (CAS 3056-17-5) and twice as effective as zidovudine (CAS 30516-87-1). STAMP was also active against pheno-typically and/or genotypically NRTI (nucleoside analog inhibitors of reverse transcriptase) -resistant HIV and inhibited the replication of 20 zidovudine-resistant clinical HIV-1 isolates with low nanomolar to subnanomolar IC50 values. Similarly, STAMP inhibited the replication of 9 genotypically NNRTI (non-nucleoside analog inhibitors of reverse transcriptase)-resistant clinical HIV-1 isolates (n = 9) with an average IC50 value of 11.2 ± 6.5 nmol/L. The remarkable potency of STAMP against clinical HIV-1 isolates with NRTI- or NNRTI-resistance warrants the further development of this promising new antiviral agent.

Zusammenfassung

In-vitro-Aktivität von Stampidin gegen primäre klinische HIV-Isolate

Die In-vitro-Aktivität von Stampidin (CAS 217178-62-6, STAMP) wurde gegen klinische HIV-1-Stämme geprüft. STAMP war in einer vergleichenden Studie gegen 10 Zidovudin-sensitive klinische HIV-1-Stämme 100-fach wirksamer als Stavudin (CAS 3056-17-5) und doppelt so wirksam wie Zidovudin (CAS 30516-87-1). STAMP war effektiv gegen phenotypisch und genotypisch NRTI (nucleoside analog inhibitors of reverse transcriptase) -resistentes HIV und inhibierte the Replikation von 20 Zidovudin-resistenten klinischen HIV-1-Stämmen mit nanomolaren oder subnanomolaren IC50-Werten. In ähnlicher Weise inhibierte STAMP die Replikation von 9 genotypisch NNRTI (non-nucleoside analog inhibitors of reverse transcriptase) -resistenten klinischen HIV-1-Stämmen mit nanomolaren IC50-Werten. Diese bemerkenswerte Wirksamkeit gegen klinische HIV-1-Stämme mit einem NRTI- oder NNRTI-resistenten Profil erfordert die weitere Entwicklung von STAMP als ein neuer antiviraler Wirkstoff.

Key words

Antiviral agents - CAS 217178-62-6 - HI-113 - Stampidine, effect on HIV isolates, in vitro studies