In vitro activity of stampidine against primary clinical human immunodeficiency virus isolates.
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 zidovudine-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 phenotypically 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.
Uckun
Fatih M
FM
Drug Discovery Program, Department of Virology, and Chemistry, Parker Hughes Cancer Center, St. Paul, MN 55113, USA. faith_uckun@ih.org
Pendergrass
Sharon
S
Qazi
Sanjive
S
Venkatachalam
Taracad K
TK
D002478:Cells, Cultured; D054306:Dideoxynucleotides; D024882:Drug Resistance, Viral; D005838:Genotype; D006678:HIV; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D009154:Mutation / Q000235:genetics / Q000502:physiology; D009504:Neutrophils / Q000821:virology; D010641:Phenotype; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D018119:Stavudine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010948:Viral Plaque Assay; D015215:Zidovudine / Q000494:pharmacology
D054306:Dideoxynucleotides; D018894:Reverse Transcriptase Inhibitors; C472384:stampidine; D019259:Lamivudine; D013938:Thymidine Monophosphate; D015215:Zidovudine; D018119:Stavudine