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• W2140478082 startingPage "5698" @default.
• W2140478082 abstract "The β-chemokine receptor CCR5 is considered to be an attractive target for inhibition of macrophage-tropic (CCR5-using or R5) HIV-1 replication because individuals having a nonfunctional receptor (a homozygous 32-bp deletion in the CCR5 coding region) are apparently normal but resistant to infection with R5 HIV-1. In this study, we found that TAK-779, a nonpeptide compound with a small molecular weight ( M r 531.13), antagonized the binding of RANTES (regulated on activation, normal T cell expressed and secreted) to CCR5-expressing Chinese hamster ovary cells and blocked CCR5-mediated Ca 2+ signaling at nanomolar concentrations. The inhibition of β-chemokine receptors by TAK-779 appeared to be specific to CCR5 because the compound antagonized CCR2b to a lesser extent but did not affect CCR1, CCR3, or CCR4. Consequently, TAK-779 displayed highly potent and selective inhibition of R5 HIV-1 replication without showing any cytotoxicity to the host cells. The compound inhibited the replication of R5 HIV-1 clinical isolates as well as a laboratory strain at a concentration of 1.6–3.7 nM in peripheral blood mononuclear cells, though it was totally inactive against T-cell line-tropic (CXCR4-using or X4) HIV-1." @default.
• W2140478082 created "2016-06-24" @default.
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• W2140478082 date "1999-05-11" @default.
• W2140478082 modified "2023-10-03" @default.
• W2140478082 title "A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity" @default.
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• W2140478082 doi "https://doi.org/10.1073/pnas.96.10.5698" @default.
• W2140478082 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/21923" @default.
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