发明名称 |
COMPOUNDS FOR INHIBITION OF HIV INFECTION BY BLOCKING HIV ENTRY |
摘要 |
A group of compounds that inhibit HIV replication by blocking HIV entry was identified. Two representative compounds, designated NB-2 and NB-64, inhibited HIV replication (p24 production) with IC<SUB>50 </SUB>values <0.5 mug/ml. It was proved that NB-2 and NB-64 are HIV entry inhibitors by targeting the HIV gp41 since: 1) they inhibited HIV-mediated cell fusion; 2) they inhibited HIV replication only when they were added to the cells less than one hour after virus addition; 3) they did not block the gp120-CD4 binding; 4) they did not interact with the coreceptor CXCR4 since they failed to block anti-CXCR4 antibody binding to CXCR4-expressing cells; 5) they blocked the formation of the gp41 core that is detected by sandwich enzyme linked immunosorbent assay (ELISA) using a conformation-specific MAb NC-1; 6) they inhibited the formation of the gp41 six-helix bundle revealed by fluorescence native-polyacrylamide gel electrophoresis (FN-PAGE); and 7) they blocked binding of D-peptide to the hydrophobic cavity within gp41 coiled coil domain, modeled by peptide IQN17. These results suggested that NB-2 and NB-64 may interact with the hydrophobic cavity and block the formation of the fusion-active gp41 coiled coil domain, resulting in inhibition of HIV-1 mediated membrane fusion and virus entry. |
申请公布号 |
EP1567491(A4) |
申请公布日期 |
2007.09.19 |
申请号 |
EP20030789757 |
申请日期 |
2003.11.12 |
申请人 |
THE NEW YORK BLOOD CENTER |
发明人 |
JIANG, SHIBO;DEBNATH, ASIM KUMAR |
分类号 |
A61K;A61K31/40;C07D207/30;C07D207/32;C07D207/327;C07D413/04;C07D417/04 |
主分类号 |
A61K |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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