| Literature DB >> 12642669 |
Kozi Ichiyama1, Sei Yokoyama-Kumakura, Yuetsu Tanaka, Reiko Tanaka, Kunitaka Hirose, Kenji Bannai, Takeo Edamatsu, Mikiro Yanaka, Yoshiaki Niitani, Naoko Miyano-Kurosaki, Hiroshi Takaku, Yoshio Koyanagi, Naoki Yamamoto.
Abstract
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 1alpha, 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 lymphocytesevere 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.Entities:
Mesh：
Substances：
Year: 2003 PMID： 12642669 PMCID： PMC153550 DOI： 10.1073/pnas.0630420100
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205