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    Novel curcuminoid-factor VIIa constructs as suppressors of tumor growth and angiogenesis
    8.
    发明申请
    Novel curcuminoid-factor VIIa constructs as suppressors of tumor growth and angiogenesis 审中-公开
    新型姜黄素因子VIIa构建成肿瘤生长和血管生成抑制因子

    公开(公告)号：US20060229239A9

    公开(公告)日：2006-10-12

    申请号：US10383898

    申请日：2003-03-07

    申请人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    发明人： Mamoru Shoji ,  James Snyder ,  Dennis Liotta ,  Aiming Sun

    IPC分类号： A61K38/17

    CPC分类号： C12Y304/21021 ,  A61K47/64 ,  A61K47/6425 ,  C07D213/63 ,  C12N9/6437

    摘要： The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. The present invention provides methods to deliver a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors. The method involves tethering the drug to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage. The present invention further provides for the synthesis of novel curcuminoid-tether-linker-factor VIIa compositions and for methods of delivery of effective doses of the novel compositions to target tumor or endothelial cells in a patient

    摘要翻译： 氟化姜黄素（3,5-双 - （2-氟亚苄基） - 哌啶-4-酮乙酸酯在阻止肿瘤细胞生长方面比顺铂高约十倍。本发明提供递送细胞毒性化合物的方法， 例如姜黄素，特别是癌细胞和滋养实体瘤的血管内皮细胞，该方法涉及将药物系在蛋白质上，例如对表面蛋白组织因子保持高亲和力的因子VIIa，在复合后，产生 异二聚体被内吞，并且药物随后通过蛋白水解切割在靶细胞内释放。本发明还提供了新型姜黄素 - 连接子 - 连接因子VIIa组合物的合成和用于将有效剂量的新组合物递送至靶 肿瘤或内皮细胞

    Novel Curcuminoid-Factor VIIA Constructs as Suppressors of Tumor Growth and Angiogenesis
    9.
    发明申请
    Novel Curcuminoid-Factor VIIA Constructs as Suppressors of Tumor Growth and Angiogenesis 审中-公开
    新型Curcuminoid因子VIIA构建体作为肿瘤生长抑制因子和血管发生

    公开(公告)号：US20090011991A1

    公开(公告)日：2009-01-08

    申请号：US12035995

    申请日：2008-02-22

    申请人： Mamoru Shoji ,  James Synder ,  Dennis Liotta ,  Aiming Sun

    发明人： Mamoru Shoji ,  James Synder ,  Dennis Liotta ,  Aiming Sun

    IPC分类号： A61K38/36 ,  A61P35/00

    CPC分类号： C12Y304/21021 ,  A61K47/6425 ,  C07D213/63 ,  C07D213/64 ,  C12N9/6437

    摘要： The fluorinated curcuminoid (3,5-bis-(2-fluorobenzylidene)-piperidin-4-one-acetate is about ten times more effective at arresting the growth of tumor cells than cisplatin. Conjugates for delivering a cytotoxic compound, such as a curcuminoid, specifically to cancer cells and to the vascular endothelial cells that nourish solid tumors, and methods of making and using thereof are described herein. The conjugate contains a cytotoxic compound bound to a protein such as in factor VIIa that retains high affinity for the surface protein tissue factor. The cytotoxic compound is bound to the protein via a linker and a hydrolyzable bond. Upon complexation, the resulting heterodimer is endocytosed and the drug is subsequently liberated inside the target cell via proteolytic cleavage.

    摘要翻译： 氟化姜黄素（3,5-双 - （2-氟亚苄基） - 哌啶-4-酮乙酸酯在阻止肿瘤细胞生长方面比顺铂高约十倍。用于递送细胞毒性化合物如姜黄素的缀合物 具体涉及癌细胞和滋养实体瘤的血管内皮细胞，本文描述了制备和使用它们的方法，该缀合物含有与蛋白质结合的细胞毒性化合物，例如对表达蛋白保持高亲和力的因子VIIa 细胞毒性化合物通过接头和可水解键与蛋白质结合，络合时，得到的异源二聚体被内吞，然后通过蛋白水解切割将药物释放到靶细胞内。