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1. 发明授权

US08283323B2 Withanolide compounds as inhibitors of fibrosis and identification of molecular targets for anti-fibrotic drug development 失效
标题翻译：助溶剂化合物作为纤维化的抑制剂和鉴定抗纤维化药物开发的分子靶标
公开(公告)号：US08283323B2
公开(公告)日：2012-10-09
申请号：US11724053
申请日：2007-03-13
申请人： Royce Mohan , Paola Bargagna-Mohan
发明人： Royce Mohan , Paola Bargagna-Mohan
IPC分类号： A61P27/02 , A61K36/185
CPC分类号： G01N33/5041 , A61K31/56 , G01N33/5038
摘要： Provided are methods for screening for drugs effective for treating fibrotic conditions. One screening method comprises exposing a cell to a test compound, monitoring the effect of the test compound on the amount or form of a cell molecule, comparing the amount or form of the cell molecule with the result obtained by treatment of the cell with an anti-fibrotic -effective amount of a withanolide compound, and selecting a drug effective for treating a fibrotic disease based on the ability of the test compound to provide the effect obtained by the withanolide compound on the cell molecule. Also provided is a method of treating a fibrotic disease comprising administering an anti-fibrotic effective amount of a withanolide compound to a mammal in need of treatment for fibrosis.
摘要翻译：提供筛选有效治疗纤维化病症的药物的方法。一种筛选方法包括将细胞暴露于测试化合物，监测测试化合物对细胞分子数量或形式的影响，将细胞分子的量或形式与通过用抗体处理细胞获得的结果进行比较 - 纤维化有效量的己内酯化合物，并且基于测试化合物提供通过所述细胞分子获得的所述作用的效果，选择有效治疗纤维化疾病的药物。还提供了一种治疗纤维化疾病的方法，其包括向需要治疗纤维化的哺乳动物施用抗纤维化有效量的己内酯化合物。

2. 发明申请

US20080032958A1 Withanolide compounds as inhibitors of fibrosis and identification of molecular targets for anti-fibrotic drug development 失效
标题翻译：助溶剂化合物作为纤维化的抑制剂和鉴定抗纤维化药物开发的分子靶标
公开(公告)号：US20080032958A1
公开(公告)日：2008-02-07
申请号：US11724053
申请日：2007-03-13
申请人： Royce Mohan , Paola Bargagna-Mohan
发明人： Royce Mohan , Paola Bargagna-Mohan
IPC分类号： A61K31/56 , A61P19/04 , C12Q1/02 , C12Q1/48
CPC分类号： G01N33/5041 , A61K31/56 , G01N33/5038
摘要： Provided are methods for screening for drugs effective for treating fibrotic conditions. One screening method comprises exposing a cell to a test compound, monitoring the effect of the test compound on the amount or form of a cell molecule, comparing the amount or form of the cell molecule with the result obtained by treatment of the cell with an anti-fibrotic-effective amount of a withanolide compound, and selecting a drug effective for treating a fibrotic disease based on the ability of the test compound to provide the effect obtained by the withanolide compound on the cell molecule. Also provided is a method of treating a fibrotic disease comprising administering an anti-fibrotic effective amount of a withanolide compound to a mammal in need of treatment for fibrosis.
摘要翻译：提供筛选有效治疗纤维化病症的药物的方法。一种筛选方法包括将细胞暴露于测试化合物，监测测试化合物对细胞分子数量或形式的影响，将细胞分子的量或形式与通过用抗体处理细胞获得的结果进行比较 - 纤维化有效量的己内酯化合物，并且基于测试化合物提供通过对侧链蛋白化合物获得的效果在细胞分子上的能力，选择有效治疗纤维化疾病的药物。还提供了一种治疗纤维化疾病的方法，其包括向需要治疗纤维化的哺乳动物施用抗纤维化有效量的己内酯化合物。

3. 发明申请

US20080207574A1 WITHANOLIDES, PROBES AND BINDING TARGETS AND METHODS OF USE THEREOF 有权
标题翻译：无色，探针和结合目标及其使用方法
公开(公告)号：US20080207574A1
公开(公告)日：2008-08-28
申请号：US11674947
申请日：2007-02-14
申请人： Royce Mohan , Paola Bargagna-Mohan , Kyung Bo Kim
发明人： Royce Mohan , Paola Bargagna-Mohan , Kyung Bo Kim
IPC分类号： A61K31/58 , G01N33/53 , C07K14/47 , C07J71/00
CPC分类号： B09C1/08 , C11D3/0084 , C11D3/188 , C11D3/382 , C11D3/39
摘要： 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.
摘要翻译：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。

4. 发明授权

US08735178B2 Withanolides, probes and binding targets and methods of use thereof 有权
标题翻译：助溶剂，探针和结合靶及其使用方法
公开(公告)号：US08735178B2
公开(公告)日：2014-05-27
申请号：US11674947
申请日：2007-02-14
申请人： Royce Mohan , Paola Bargagna-Mohan , Kyung Bo Kim
发明人： Royce Mohan , Paola Bargagna-Mohan , Kyung Bo Kim
IPC分类号： G01N33/532 , G01N33/534 , G01N33/533
CPC分类号： B09C1/08 , C11D3/0084 , C11D3/188 , C11D3/382 , C11D3/39
摘要： 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.
摘要翻译：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。

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