中科微点-全球专利检索

  1. Login
  2. Sign Up

Search Results

58 records (took 0.015 seconds)

    GELDANAMYCINS AND THEIR QUINONE MOIETIES INHIBIT CANCER BY ACTING ON MITOCHONDRIAL VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) PROTEIN
    2.
    发明申请
    GELDANAMYCINS AND THEIR QUINONE MOIETIES INHIBIT CANCER BY ACTING ON MITOCHONDRIAL VOLTAGE-DEPENDENT ANION CHANNEL (VDAC) PROTEIN 审中-公开
    通过采用麻醉电压依赖性阴离子通道（VDAC）蛋白，GELDANAMYCINS及其喹诺酮抑制剂

    公开(公告)号：WO2007134328A3

    公开(公告)日：2008-12-04

    申请号：PCT/US2007068988

    申请日：2007-05-15

    Applicant: VAN ANDEL RES INST ,  UNIV MICHIGAN STATE ,  UNIV TENNESSEE EAST ,  XIE QIAN ,  WENKERT DAVID ,  SHEN YUCHAI ,  VANDE WOUDE GEORGE F ,  HAY RICK ,  WONDERGEM ROBERT

    Inventor： XIE QIAN ,  WENKERT DAVID ,  SHEN YUCHAI ,  VANDE WOUDE GEORGE F ,  HAY RICK ,  WONDERGEM ROBERT

    IPC: C07D345/00 ,  C07J41/00

    CPC classification number: C07J41/00 ,  C07C205/22 ,  C07C205/37 ,  C07C233/41 ,  C07D203/14 ,  C07D225/06 ,  C07D403/04 ,  C07D498/04

    Abstract: Derivatives of geldanamycin (GA), a benzoquinone ansamycin antibiotic, are in clinical trials as anticancer drugs. While, at nanomolar concentrations, these drugs are known to target HSP90 chaperone activity, second anticancer activity that inhibits HGF/SF-mediated tumor cell invasion at nanomolar concentrations has been found. Disclosed is the identification of the outer membrane mitochondrial voltage-dependent anion channel (VDAC) protein, a component of the permeability transition pore (PTP), as a novel GA binding protein and a demonstration that GA inhibits membrane potential at picomolar levels. Uubiquinone 0 and decyl-ubiquinone, known benzoquinone inhibitors of mitochondrial PTP function like GA, inhibit HGF/SF induced urokinase (uPA) plasmin protease activation and HGF/SF activated membrane currents in whole-cell voltage clamp assays, with GA blocking at picomolar levels. The results disclosed regarding mechanism of action are a major step in harnessing such drugs for use for treating highly invasive cancers like glioblastoma.

    Abstract translation: 格列尔霉素（GA）的衍生物，苯醌安莎霉素抗生素，作为抗癌药物进行临床试验。 而在纳摩尔浓度下，已知这些药物靶向HSP90分子伴侣活性，已经发现了以纳摩尔浓度抑制HGF / SF介导的肿瘤细胞侵袭的第二抗癌活性。 公开了作为新型GA结合蛋白的外膜线粒体电压依赖性阴离子通道（VDAC）蛋白（通透性转换孔（PTP）的组分）的鉴定，并证明GA在皮摩尔水平抑制膜电位。 Uubiquinone 0和癸基泛醌，线粒体PTP功能的已知苯醌抑制剂如GA，在全细胞电压钳测定中抑制HGF / SF诱导的尿激酶（uPA）纤溶酶蛋白酶激活和HGF / SF活化的膜电流，具有在皮摩尔水平的GA阻断 。 披露的关于作用机制的结果是利用这些药物用于治疗高侵袭性癌症如胶质母细胞瘤的主要步骤。

    BICYCLIC AMIDES AS INHIBITORS OF ACYL-COENZYME A: CHOLESTEROL ACYL TRANSFERASE
    7.
    发明申请
    BICYCLIC AMIDES AS INHIBITORS OF ACYL-COENZYME A: CHOLESTEROL ACYL TRANSFERASE 审中-公开
    作为ACYL-COENZYME A的抑制剂的双酚A：胆固醇ACYL转移

    公开(公告)号：WO1992018462A1

    公开(公告)日：1992-10-29

    申请号：PCT/US1992002662

    申请日：1992-04-09

    Applicant: SCHERING CORPORATION ,  CLADER, John, W. ,  FEVIG, Thomas ,  VACCARO, Wayne ,  BERGER, Joel, G.

    Inventor： SCHERING CORPORATION

    IPC: C07C233/23

    CPC classification number: C07D213/75 ,  C07C233/06 ,  C07C233/14 ,  C07C233/23 ,  C07C233/41 ,  C07C2602/08 ,  C07C2602/10 ,  C07D311/68

    Abstract: Novel bicyclic amides of formula (I), wherein Ar?1 and Ar2¿ are phenyl, R2-substituted phenyl, heteroaryl or R2-substituted heteroaryl, wherein R2 is 1 to 3 substituents independentlyselected from the group consisting of halogeno, hydroxy, lower alkyl, lower alkoxy, nitro, amino, lower alkylamino and lower dialkylamino; X, Y and Z are -CH¿2?-, -CH(alkyl)-, -C(alkyl)2-, -NH-, -N(alkyl)-, -O- or -SOr-, wherein r is 0, 1 or 2, and m, n and p are 0 or 1; R?1¿ is an alkyl chain of 1 to 25 carbon atoms; an alkyl chain substituted by one or more optionally substituted phenyl or heteroaryl groups; an alkyl chain -0-, -S0¿r?-, phenylene, R?2¿-substituted phenylene, heteroarylene or R2-substituted heteroarylene groups; an interrupted alkyl chain substituted by one or more optionally substituted phenyl or heteroaryl groups; an alkyl chain of 4 to 25 carbon atoms, interrupted by one or more -NH-, -C(O)- or -N(lower alkyl)- groups; an interrupted alkyl chain of 4 to 25 carbon atoms substituted by one or more phenyl, R2-substituted phenyl, heteroaryl or R2-substituted heteroaryl groups; a diphenylamino group; a di-(R2-substituted phenyl)amino group; a diheteroarylamino group ; or a di-(R2-substituted heteroaryl)amino group; or a pharmaceutically acceptable salt thereof, useful in the treatmeent of artherosclerosis are disclosed.

Patent Agency Ranking