Inhibition of HIV-1 replication by a nonnucleoside reverse transcriptase inhibitor
| Autor: | Vincent J. Merluzzi, Karl D. Hargrave, Mark Labadia, Karl Grozinger, Mark Skoog, Joseph C. Wu, Cheng-Kon Shih, Kristine Eckner, Susan Hattox, Julian Adams, Alan S. Rosenthal, Ronald Faanes, Robert J. Eckner, Richard A. Koup, John L. Sullivan |
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| Rok vydání: | 1990 |
| Předmět: |
DNA polymerase
Pyridines In situ hybridization Virus Replication Antiviral Agents Cell Line chemistry.chemical_compound medicine Animals Humans Nevirapine Nucleic Acid Synthesis Inhibitors Multidisciplinary Reverse-transcriptase inhibitor Deoxyguanosine triphosphate biology Molecular Structure virus diseases Virology Molecular biology Reverse transcriptase In vitro Discovery and development of non-nucleoside reverse-transcriptase inhibitors Kinetics chemistry Cell culture biology.protein HIV-1 Reverse Transcriptase Inhibitors medicine.drug |
| Zdroj: | Science (New York, N.Y.). 250(4986) |
| ISSN: | 0036-8075 |
| Popis: | A series of dipyridodiazepinones have been shown to be potent inhibitors of human immunodeficiency virus-1 (HIV-1) reverse transcriptase (RT). One compound, BI-RG-587, had a Ki of 200 nanomolar for inhibition of HIV-1 RT that was noncompetitive with respect to deoxyguanosine triphosphate. BI-RG-587 was specific for HIV-1 RT, having no effect on feline and simian RT or any mammalian DNA polymerases. BI-RG-587 inhibited HIV-1 replication in vitro as demonstrated by in situ hybridization, inhibition of protein p24 production, and the lack of syncytia formation in cultured human T cell lines and freshly isolated human peripheral blood lymphocytes. Cytotoxicity studies of BI-RG-587 on human cells showed a high therapeutic index (greater than 8000) in culture. |
| Databáze: | OpenAIRE |
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