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    • 82. 发明申请
    • WITHANOLIDES, PROBES AND BINDING TARGETS AND METHODS OF USE THEREOF
    • 无色,探针和结合目标及其使用方法
    • US20080207574A1
    • 2008-08-28
    • US11674947
    • 2007-02-14
    • Royce MohanPaola Bargagna-MohanKyung Bo Kim
    • Royce MohanPaola Bargagna-MohanKyung Bo Kim
    • A61K31/58G01N33/53C07K14/47C07J71/00
    • B09C1/08C11D3/0084C11D3/188C11D3/382C11D3/39
    • Novel withanolide chemical genetic probes identify the in vivo binding target of withaferin A, which is the intermediate filament type III protein vimentin. In addition, a withanolide-based small molecule screening method screens drug candidates that target intermediate filament type III proteins. The method includes introducing a tagged linker covalently bonded to the withanolide molecule to form a withanolide probe. Better or alternative small molecule compounds as potential drug candidates can be generated based on their likely affinity for the determined binding site in vimentin. The affinity labeled withanolide can also be used to find intermediate filament-associated proteins using chemical proteomics by extracting proteins from cells that were exposed to withanolide-biotin analog. The withanolide probes can be used to monitor expression of vimentin, in tumor samples or other diseased tissues. Withaferin analogs can be used as a treatment for diverse vimentin-associated disorders, such as cancers, angiofibrotic diseases, and chronic inflammation.
    • 新型的腺苷酸化学遗传探针鉴定了与卵白蛋白A的体内结合靶,其是中间丝型III型蛋白波形蛋白。 另外,以基于羊毛脂的小分子筛选方法筛选靶向中间丝III型蛋白质的候选药物。 所述方法包括引入共价键合到所述己内酯分子上的标记接头以形成己内酯探针。 可以基于它们对波形蛋白中所确定的结合位点的可能亲和力来产生作为潜在药物候选物的更好或替代的小分子化合物。 使用化学蛋白质组学技术,通过从暴露于脱乙酰壳多糖 - 生物素类似物的细胞中提取蛋白质,也可以使用标记有烯醇化物的亲和力来发现中间丝相关蛋白。 索尔诺德探针可用于监测波形蛋白在肿瘤样品或其他患病组织中的表达。 嗜铬蛋白类似物可用作治疗多种波形蛋白相关疾病,例如癌症,血管纤维化疾病和慢性炎症。