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    • 9. 发明授权
    • Materials and methods for sensitizing multidrug resistant cells
    • 敏感多药耐药细胞的材料和方法
    • US08455252B2
    • 2013-06-04
    • US13125530
    • 2009-10-24
    • Jian-Ting ZhangJing QiHui PengZizheng Dong
    • Jian-Ting ZhangJing QiHui PengZizheng Dong
    • A61K31/425A61K31/54
    • A61K31/425A61K31/54
    • Disclosed herein are materials and methods for sensitizing multidrug resistant cancer cells that express ABCG2 and related proteins members of a family of ATP-binding transporter superfamily that mediate drug efflux found in some types of multidrug resistant cancer cells. A series of compounds, including (N-(4-chlorophenyl)-2-[(6-{[4,6-di(4-morpholinyl)-1,3,5-tri-azin-2-yl]amino}-1,3-benzothiazol-2-yl)sulfanyl]acetamide), specifically inhibits ABCG2 and can be used to boost the bio-avail-ability of one or more effective cancer killing drugs, making it possible to use certain widely used chemotherapeutic reagent to treat multidrug resistance cancers. Using these compounds in combination with chemotherapeutic drugs that are substrates for ABCG2 and related proteins may also find utility in treating cancer cells that are not currently identified as multi-drug resistant. Additionally, these compounds appear to accelerate the intercellular degradation of ABCG2 and related proteins. They are not toxic to animals at levels at which they effect the activity of ABCG2 expressed in multi-drug resistant cancer lines.
    • 本文公开了用于敏化多药耐药性癌细胞的材料和方法,所述多药耐药性癌细胞表达ABCG2和ATP结合转运蛋白超家族的相关蛋白质成员,其介导某些类型的多重耐药性癌细胞中发现的药物流出。 一系列化合物,包括(N-(4-氯苯基)-2 - [(6 - {[4,6-二(4-吗啉基)-1,3,5-三氮杂萘-2-基]氨基} -1,3-苯并噻唑-2-基)硫烷基]乙酰胺),特异性抑制ABCG2,可用于提高一种或多种有效的癌症杀伤药物的生物利用度,使得可以使用某些广泛使用的化学治疗试剂 治疗多药耐药性癌症。 将这些化合物与作为ABCG2和相关蛋白质的底物的化学治疗药物组合也可用于治疗目前未被鉴定为多重耐药性的癌细胞。 此外,这些化合物似乎加速了ABCG2和相关蛋白的细胞间降解。 它们在影响多药耐药性癌细胞系中表达的ABCG2活性的水平下对动物无毒性。