A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity
| Autor: | Naoki Yamamoto, Yoshiaki Niitani, Kunitaka Hirose, Yoshio Koyanagi, Sei Yokoyama-Kumakura, Yuetsu Tanaka, Reiko Tanaka, Kozi Ichiyama, Naoko Miyano-Kurosaki, Mikiro Yanaka, Takeo Edamatsu, Kenji Bannai, Hiroshi Takaku |
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| Rok vydání: | 2003 |
| Předmět: |
Receptors
CXCR4 Anti-HIV Agents Pyridines Chemokine receptor CCR5 T-Lymphocytes Mice SCID C-C chemokine receptor type 6 Arginine CXCR3 Mice Chemokine receptor Tumor Cells Cultured Animals Humans CCL17 Lymphocytes CXC chemokine receptors Rats Wistar Multidisciplinary biology Biological Sciences Molecular biology Rats CXCL2 Intestinal Absorption HIV-1 biology.protein CCL21 |
| Zdroj: | Proceedings of the National Academy of Sciences. 100:4185-4190 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0630420100 |
| Popis: | A low molecular weight nonpeptide compound, KRH-1636, efficiently blocked replication of various T cell line-tropic (X4) HIV type 1 (HIV-1) in MT-4 cells and peripheral blood mononuclear cells through the inhibition of viral entry and membrane fusion via the CXC chemokine receptor (CXCR)4 coreceptor but not via CC chemokine receptor 5. It also inhibited binding of the CXC chemokine, stromal cell-derived factor 1α, to CXCR4 specifically and subsequent signal transduction. KRH-1636 prevented monoclonal antibodies from binding to CXCR4 without down-modulation of the coreceptor. The inhibitory effect against X4 viral replication by KRH-1636 was clearly reproduced in the human peripheral blood lymphocyte/severe combined immunodeficiency mouse system. Furthermore, this compound was absorbed into the blood after intraduodenal administration as judged by anti-HIV-1 activity and liquid chromatography MS in the plasma. Thus, KRH-1636 seems to be a promising agent for the treatment of HIV-1 infection. |
| Databáze: | OpenAIRE |
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