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    Enzyme inhibition
    1.
    发明授权
    Enzyme inhibition 有权
    酶抑制

    公开(公告)号：US06831099B1

    公开(公告)日：2004-12-14

    申请号：US09569748

    申请日：2000-05-11

    申请人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Ny Sin ,  Kyung Bo Kim

    发明人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Ny Sin ,  Kyung Bo Kim

    IPC分类号： A01N4320

    CPC分类号： C07K5/1016 ,  C07K5/1008 ,  C07K5/101 ,  C07K7/06

    摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like and PGPH activities of the 20S proteasome can be selectively inhibited with the inventive compounds. The peptide-based compounds include an electron withdrawing group adjacent to the ring functionality, and the peptide include at least three peptide units. Among other therapeutic utilities, the peptide-based compounds exhibit anti-inflammatory and inhibition of cell proliferation, involving therapeutic applications for these compounds.

    摘要翻译： 包括含杂原子的三元环的基于肽的化合物有效地选择性地抑制N末端亲核试剂（Ntn）水解酶的比活性。 具有多种活性的那些Ntn的活性可被所描述的化合物差别地抑制。 例如，本发明化合物可以选择性地抑制20S蛋白酶体的胰凝乳蛋白酶样和PGPH活性。 基于肽的化合物包括与环官能团相邻的吸电子基团，并且肽包括至少三个肽单元。 在其他治疗用途中，基于肽的化合物表现出抗炎和抑制细胞增殖，涉及这些化合物的治疗应用。

    Enzyme inhibition
    2.
    发明授权
    Enzyme inhibition 有权
    酶抑制

    公开(公告)号：US07476650B2

    公开(公告)日：2009-01-13

    申请号：US10871752

    申请日：2004-06-17

    申请人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Kyung Bo Kim

    发明人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Kyung Bo Kim

    IPC分类号： A01N43/02 ,  A61K38/00

    CPC分类号： C07K5/1016 ,  C07K5/1008 ,  C07K5/101 ,  C07K7/06

    摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like and PGPH activities of the 20S proteasome can be selectively inhibited with the inventive compounds. The peptide-based compounds include an electron withdrawing group adjacent to the ring functionality, and the peptide include at least three peptide units. Among other therapeutic utilities, the peptide-based compounds exhibit anti-inflammatory and inhibition of cell proliferation, involving therapeutic applications for these compounds.

    摘要翻译： 包括含杂原子的三元环的基于肽的化合物有效地选择性地抑制N末端亲核试剂（Ntn）水解酶的比活性。 具有多种活性的那些Ntn的活性可被所描述的化合物差别地抑制。 例如，本发明化合物可以选择性地抑制20S蛋白酶体的胰凝乳蛋白酶样和PGPH活性。 基于肽的化合物包括与环官能团相邻的吸电子基团，并且肽包括至少三个肽单元。 在其他治疗用途中，基于肽的化合物表现出抗炎和抑制细胞增殖，涉及这些化合物的治疗应用。

    Enzyme inhibition
    3.
    发明申请
    Enzyme inhibition 审中-公开

    公开(公告)号：US20090099097A1

    公开(公告)日：2009-04-16

    申请号：US12291236

    申请日：2008-11-07

    申请人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Kyung Bo Kim

    发明人： Craig M. Crews ,  Mikael Elofsson ,  Ute Splittgerber ,  Kyung Bo Kim

    IPC分类号： A61K38/08

    CPC分类号： C07K5/1016 ,  C07K5/1008 ,  C07K5/101 ,  C07K7/06

    摘要： Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like and PGPH activities of the 20S proteasome can be selectively inhibited with the inventive compounds. The peptide-based compounds include an electron withdrawing group adjacent to the ring functionality, and the peptide include at least three peptide units. Among other therapeutic utilities, the peptide-based compounds exhibit anti-inflammatory and inhibition of cell proliferation, involving therapeutic applications for these compounds.

    EPOXYKETONE-BASED IMMUNOPROTEASOME INHIBITORS
    4.
    发明申请
    EPOXYKETONE-BASED IMMUNOPROTEASOME INHIBITORS 失效
    基于环氧酮的免疫抑制剂

    公开(公告)号：US20080064659A1

    公开(公告)日：2008-03-13

    申请号：US11531129

    申请日：2006-09-12

    申请人： Kyung Bo Kim ,  Yik Khuan Ho

    发明人： Kyung Bo Kim ,  Yik Khuan Ho

    IPC分类号： A61K31/695 ,  C07F7/02 ,  C07D303/36

    CPC分类号： C07D303/24 ,  C07D407/12

    摘要： An efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative, is provided, which includes the synthesis of the intermediate compound, a hydroxymethyl-substituted enone. In addition, a method is provided for synthesizing inhibitors, which includes PI′-modified analogues. These analogues selectively bind to a major immunoproteasome catalytic subunit LMP2 and inactivate its proteolytic activity in a method of treating diseases, including myeloma and other cancers, Huntington's disease and Alzheimer's disease.

    摘要翻译： 提供了一种用于制备活性离子霉素衍生物的二氢异苯菌霉素的有效新途径，其包括中间体化合物的羟基甲基取代的烯酮的合成。 此外，提供了一种合成抑制剂的方法，其包括PI'-修饰的类似物。 这些类似物选择性地结合主要的免疫蛋白酶体催化亚基LMP2，并且在治疗疾病包括骨髓瘤和其他癌症亨廷顿病和阿尔茨海默氏病的方法中使其蛋白水解活性失活。

    Epoxyketone-based immunoproteasome inhibitors
    6.
    发明授权
    Epoxyketone-based immunoproteasome inhibitors 失效
    基于环氧酮的免疫蛋白酶体抑制剂

    公开(公告)号：US07642369B2

    公开(公告)日：2010-01-05

    申请号：US11531129

    申请日：2006-09-12

    申请人： Kyung Bo Kim ,  Yik Khuan Ho

    发明人： Kyung Bo Kim ,  Yik Khuan Ho

    IPC分类号： C07C269/00

    CPC分类号： C07D303/24 ,  C07D407/12

    摘要： An efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative, is provided, which includes the synthesis of the intermediate compound, a hydroxymethyl-substituted enone. In addition, a method is provided for synthesizing inhibitors, which includes PI′-modified analogues. These analogues selectively bind to a major immunoproteasome catalytic subunit LMP2 and inactivate its proteolytic activity in a method of treating diseases, including myeloma and other cancers, Huntington's disease and Alzheimer's disease.

    摘要翻译： 提供了一种用于制备活性离子霉素衍生物的二氢异苯菌霉素的有效新途径，其包括中间体化合物的羟基甲基取代的烯酮的合成。 此外，提供了一种合成抑制剂的方法，其包括PI'-修饰的类似物。 这些类似物选择性地结合主要的免疫蛋白酶体催化亚基LMP2，并且在治疗疾病包括骨髓瘤和其他癌症亨廷顿病和阿尔茨海默氏病的方法中使其蛋白水解活性失活。

    WITHANOLIDES, PROBES AND BINDING TARGETS AND METHODS OF USE THEREOF
    7.
    发明申请
    WITHANOLIDES, PROBES AND BINDING TARGETS AND METHODS OF USE THEREOF 有权
    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。

    Withanolides, probes and binding targets and methods of use thereof
    8.
    发明授权
    Withanolides, probes and binding targets and methods of use thereof 有权
    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。