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    • 2. 发明申请
    • ANTI-VIRAL COMPOSITIONS COMPRISING HETEROCYCLIC SUBSTITUTED PHENYL FURANS AND RELATED COMPOUNDS
    • 包含杂环取代的苯甲酸和相关化合物的抗病毒组合物
    • WO2006138118A2
    • 2006-12-28
    • PCT/US2006021993
    • 2006-06-06
    • NEW YORK BLOOD CT INCJIANG SHIBODEBNATH ASIM KUMARLU HONG
    • JIANG SHIBODEBNATH ASIM KUMARLU HONG
    • A61K31/53A61K31/427A61K31/4439A61K31/496A61K31/497A61K31/501
    • A61K31/427A61K31/4439A61K31/496A61K31/497A61K31/501A61K31/53
    • A group of compounds that inhibit HIV replication by blocking HIV entry was identified. One representative compound, designated NB-206, and its analogs inhibited HIV replication (p24 production) with IC50 values at nanomolar levels. It was proved that NB-206 and its analogs 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 blocked the formation of the gp41 core that is detected by sandwich enzyme linked immunosorbent assay (ELISA) using a conformation- specific MAb NC-I; and 4) they inhibited the formation of the gp41 six-helix bundle revealed by fluorescence native-polyacrylamide gel electrophoresis (FN-PAGE) . These results suggested that NB-206 and its analogs may interact with the hydrophobic cavity and block the formation of the fusion- active gp41 coiled coil domain, resulting in inhibition of HIV-I mediated membrane fusion and virus entry.
    • 鉴定了一组通过阻断HIV进入而抑制HIV复制的化合物。 一个代表性的化合物,称为NB-206及其类似物,其抑制HIV复制(p24产生),IC50值为纳摩尔水平。 证实NB-206及其类似物是通过靶向HIV gp41的HIV进入抑制因子,因为:1)它们抑制HIV介导的细胞融合; 2)只有当病毒加入不到1小时后,才能抑制HIV复制; 3)它们阻断了使用构象特异性MAb NC-1通过夹心酶联免疫吸附测定(ELISA)检测到的gp41核心的形成; 和4)它们抑制由荧光天然 - 聚丙烯酰胺凝胶电泳(FN-PAGE)显示的gp41六螺旋束的形成。 这些结果表明,NB-206及其类似物可能与疏水腔相互作用并阻断融合活性gp41卷曲螺旋结构域的形成,导致HIV-1介导的膜融合和病毒进入的抑制。