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    INHIBITION STAT-1
    3.
    发明申请
    INHIBITION STAT-1 审中-公开
    抑制STAT-1

    公开(公告)号：US20090203767A1

    公开(公告)日：2009-08-13

    申请号：US12358088

    申请日：2009-01-22

    申请人： Markus Hecker ,  Andreas H. Wagner

    发明人： Markus Hecker ,  Andreas H. Wagner

    IPC分类号： A61K31/7088 ,  A61P9/00

    CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C12N2310/111 ,  C12N2310/13

    摘要： The present invention relates to inhibitors of the transcription factor STAT-1, their use as therapeutic means as well as their use for the prevention or therapy of cardio-vascular complications like restenosis after percutaneous angioplasty or stenosis of venous bypasses, the graft versus host reaction, the ischemia/refusion-related damage in the context of surgical interventions and organ transplantation respectively, immunological hypersensitivity reactions, in particular the allergic rhinitis, the drug and food allergies, in particular urticaria and celiac disease (sprue), contact eczema and the immune complex diseases, in particular alveolitis, arthritis, glomerulonephritis and allergic vasculitis, inflammatory chondro- and osteopathies, in particular arthrosis, gout, ostitis and osteomyelitis, polyneuritis as well as acute and subacute respectively, infection contingent and in particular post-infectious inflammatory diseases, in particular bronchitis, endocarditis, hepatitis, myocarditis, nephritis, pericarditis, peritonitis and pancreatitis, including the septic shock.

    摘要翻译： 本发明涉及转录因子STAT-1的抑制剂，它们作为治疗方法的用途以及它们用于预防或治疗心血管并发症的用途，如经皮血管成形术或静脉旁路狭窄后的再狭窄，移植物抗宿主反应 ，外科手术和器官移植背景下的缺血/重塑相关损伤，免疫超敏反应，特别是过敏性鼻炎，药物和食物过敏症，特别是荨麻疹和乳糜泻（口腔），接触性湿疹和免疫 复杂疾病，特别是肺泡炎，关节炎，肾小球性肾炎和过敏性血管炎，炎性软骨和骨病，特别是关节病，痛风，口鼻炎和骨髓炎，多发性神经炎以及急性和亚急性感染，特别是感染后炎症性疾病， 特别是支气管炎，心内膜炎，肝炎，肌内 心包炎，肾炎，心包炎，腹膜炎和胰腺炎，包括败血性休克。

    Steroidogenesis modified cells and methods for screening for endocrine disrupting chemicals
    4.
    发明授权
    Steroidogenesis modified cells and methods for screening for endocrine disrupting chemicals 有权
    类固醇生成修饰细胞和筛选内分泌干扰物质的方法

    公开(公告)号：US08501401B2

    公开(公告)日：2013-08-06

    申请号：US13619236

    申请日：2012-09-14

    申请人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    发明人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    IPC分类号： C12Q1/68

    CPC分类号： G01N33/5008 ,  G01N33/743

    摘要： An isolated steroidogenesis modified cell comprising one or more steroid biosynthesis knock down nucleic acid operatively linked to a promoter, wherein the steroid biosynthesis knock down nucleic acid reduces the expression of a gene selected from the group CYP21A2, CYP11A1, CYP17A1, CYP19A1, 3-βHSD1, 3-βHSD2, 17-βHSD1, StAR, HMGR, CYP11B2, CYP11B1, 5α-Reductase 2, SULT1E1, CYP3A4 and UTG1A1, wherein the cell comprises reduced expression of one or more of said genes. The cells are useful for identifying endocrine disruptors. Accordingly, the disclosure includes in a further aspect a screening assay for identifying an endocrine disruptor comprising: a) contacting a cell described herein with a test substance; b) determining a level of at least one steroid or steroidogenic gene mRNA or enzyme activity; wherein a modulation in the level of the at least one steroid or steroidogenic gene mRNA or enzyme activity compared to a control is indicative that the test substance is an endocrine disruptor.

    摘要翻译： 包含一种或多种类固醇生物合成的分离的类固醇生成修饰的细胞敲除与启动子有效连接的核酸，其中类固醇生物合成敲低核酸降低了选自CYP21A2，CYP11A1，CYP17A1，CYP19A1,3-βHSD1的基因的表达 ，3-βHSD2,17-βHSD1，StAR，HMGR，CYP11B2，CYP11B1,5α-还原酶2，SULT1E1，CYP3A4和UTG1A1，其中所述细胞包含一种或多种所述基因的降低的表达。 细胞可用于鉴定内分泌干扰物。 因此，本公开在另一方面包括用于鉴定内分泌干扰物的筛选测定法，其包括：a）使本文所述的细胞与测试物质接触; b）确定至少一种类固醇或类固醇基因mRNA或酶活性的水平; 其中与对照相比，所述至少一种类固醇或类固醇基因mRNA或酶活性水平的调节指示所述测试物质是内分泌干扰物。

    STEROIDOGENESIS MODIFIED CELLS AND METHODS FOR SCREENING FOR ENDOCRINE DISRUPTING CHEMICALS
    5.
    发明申请
    STEROIDOGENESIS MODIFIED CELLS AND METHODS FOR SCREENING FOR ENDOCRINE DISRUPTING CHEMICALS 有权
    STEROIDOGENESIS改良细胞和筛选化学品内切蛋白的方法

    公开(公告)号：US20130011850A1

    公开(公告)日：2013-01-10

    申请号：US13619236

    申请日：2012-09-14

    申请人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    发明人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    IPC分类号： C12Q1/68 ,  C12Q1/02 ,  G01N27/62 ,  G01N33/566

    CPC分类号： G01N33/5008 ,  G01N33/743

    摘要： An isolated steroidogenesis modified cell comprising one or more steroid biosynthesis knock down nucleic acid operatively linked to a promoter, wherein the steroid biosynthesis knock down nucleic acid reduces the expression of a gene selected from the group CYP21A2, CYP11A1, CYP17A1, CYP19A1, 3-βHSD1, 3-βHSD2, 17-βHSD1, StAR, HMGR, CYP11B2, CYP11B1, 5α-Reductase 2, SULT1E1, CYP3A4 and UTG1A1, wherein the cell comprises reduced expression of one or more of said genes. The cells are useful for identifying endocrine disruptors. Accordingly, the disclosure includes in a further aspect a screening assay for identifying an endocrine disruptor comprising: a) contacting a cell described herein with a test substance; b) determining a level of at least one steroid or steroidogenic gene mRNA or enzyme activity; wherein a modulation in the level of the at least one steroid or steroidogenic gene mRNA or enzyme activity compared to a control is indicative that the test substance is an endocrine disruptor.

    摘要翻译： 分离的类固醇生成修饰细胞，其包含一种或多种类固醇生物合成，敲除与启动子有效连接的核酸，其中类固醇生物合成敲低核酸降低了选自CYP21A2，CYP11A1，CYP17A1，CYP19A1，3-＆bgr的基因的表达 HSD1,38和HSG2，HSD1，StAR，HMGR，CYP11B2，CYP11B1,5α-还原酶2，SULT1E1，CYP3A4和UTG1A1，其中所述细胞包含一种或多种所述基因的降低的表达。 细胞可用于鉴定内分泌干扰物。 因此，本公开在另一方面包括用于鉴定内分泌干扰物的筛选测定法，其包括：a）使本文所述的细胞与测试物质接触; b）确定至少一种类固醇或类固醇基因mRNA或酶活性的水平; 其中与对照相比，所述至少一种类固醇或类固醇基因mRNA或酶活性水平的调节指示所述测试物质是内分泌干扰物。

    STEROIDOGENESIS MODIFIED CELLS AND METHODS FOR SCREENING FOR ENDOCRINE DISRUPTING CHEMICALS
    8.
    发明申请
    STEROIDOGENESIS MODIFIED CELLS AND METHODS FOR SCREENING FOR ENDOCRINE DISRUPTING CHEMICALS 失效
    STEROIDOGENESIS改良细胞和筛选化学品内切蛋白的方法

    公开(公告)号：US20110065114A1

    公开(公告)日：2011-03-17

    申请号：US12883929

    申请日：2010-09-16

    申请人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    发明人： Xiaowei Zhang ,  Markus Hecker ,  John P. Giesy

    IPC分类号： C12Q1/68 ,  C12N5/10 ,  G01N33/566 ,  C12Q1/02 ,  G06F19/00

    CPC分类号： G01N33/5008 ,  G01N33/743

    摘要： An isolated steroidogenesis modified cell comprising one or more steroid biosynthesis knock down nucleic acid operatively linked to a promoter, wherein the steroid biosynthesis knock down nucleic acid reduces the expression of a gene selected from the group CYP21A2, CYP11A1, CYP17A1, CYP19A1, 3-βHSD1, 3-βHSD2, 17-βHSD1, StAR, HMGR, CYP11B2, CYP11B1, 5α-Reductase 2, SULT1E1, CYP3A4 and UTG1A1, wherein the cell comprises reduced expression of one or more of said genes. The cells are useful for identifying endocrine disruptors. Accordingly, the disclosure includes in a further aspect a screening assay for identifying an endocrine disruptor comprising: a) contacting a cell described herein with a test substance; b) determining a level of at least one steroid or steroidogenic gene mRNA or enzyme activity; wherein a modulation in the level of the at least one steroid or steroidogenic gene mRNA or enzyme activity compared to a control is indicative that the test substance is an endocrine disruptor.

    摘要翻译： 分离的类固醇生成修饰细胞，其包含一种或多种类固醇生物合成，敲除与启动子有效连接的核酸，其中类固醇生物合成敲低核酸降低了选自CYP21A2，CYP11A1，CYP17A1，CYP19A1，3-＆bgr的基因的表达 HSD1,38和HSG2，HSD1，StAR，HMGR，CYP11B2，CYP11B1,5α-还原酶2，SULT1E1，CYP3A4和UTG1A1，其中所述细胞包含一种或多种所述基因的降低的表达。 细胞可用于鉴定内分泌干扰物。 因此，本公开在另一方面包括用于鉴定内分泌干扰物的筛选测定法，其包括：a）使本文所述的细胞与测试物质接触; b）确定至少一种类固醇或类固醇基因mRNA或酶活性的水平; 其中与对照相比，所述至少一种类固醇或类固醇基因mRNA或酶活性水平的调节指示所述测试物质是内分泌干扰物。

    Double stranded DNA inhibitor of IRF-1 activity
    9.
    发明授权
    Double stranded DNA inhibitor of IRF-1 activity 失效
    IRF-1活性双链DNA抑制剂

    公开(公告)号：US07524949B2

    公开(公告)日：2009-04-28

    申请号：US10398592

    申请日：2001-10-04

    申请人： Markus Hecker ,  Andreas H. Wagner

    发明人： Markus Hecker ,  Andreas H. Wagner

    IPC分类号： C07H21/04 ,  A61K31/70

    CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C12N2310/13 ,  C12N2310/315 ,  C12N2310/341

    摘要： The present invention refers to inhibitors of the transcription factors IRF-1, their use as therapeutic agents as well as their use for prevention and therapy of cardiovascular complications like re-stenosis after percutaneous angioplasty or stenosis of venous bypasses, chronic (transplant arteriosclerosis or vasculopathy) or acute transplant rejection, graft versus host disease (GVHD), immunological hypersensitivity reactions (allergies), particularly bronchial asthma and atopic dermatitis, chronic recurrent inflammatory diseases, particularly ulcerative colitis and Crohn's disease, psoriasis and sarcoidosis, as well as autoimmune diseases, particularly diabetes mellitus, multiple sclerosis, collagenoses (e. g. systemic lupus erythematodes), rheumatoid arthritis and vasculotids.

    摘要翻译： 本发明涉及转录因子IRF-1的抑制剂，它们作为治疗剂的用途以及其用于预防和治疗心血管并发症的用途，如经皮血管成形术或静脉旁路狭窄，慢性（移植物动脉硬化或血管病变）之后的再狭窄 ）或急性移植排斥反应，移植物抗宿主病（GVHD），免疫超敏反应（过敏），特别是支气管哮喘和特应性皮炎，慢性复发性炎症疾病，特别是溃疡性结肠炎和克罗恩病，牛皮癣和结节病，以及自身免疫性疾病， 特别是糖尿病，多发性硬化症，胶原病（例如系统性红斑狼疮），类风湿关节炎和血管病变。

    Inhibition of STAT-1
    10.
    发明授权
    Inhibition of STAT-1 失效
    抑制STAT-1

    公开(公告)号：US07485628B2

    公开(公告)日：2009-02-03

    申请号：US10491758

    申请日：2002-10-02

    申请人： Markus Hecker ,  Andreas H. Wagner

    发明人： Markus Hecker ,  Andreas H. Wagner

    IPC分类号： A61K31/70 ,  C07H21/04

    CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C12N2310/111 ,  C12N2310/13

    摘要： The present invention relates to inhibitors of the transcription factor STAT-1, their use as therapeutic means as well as their use for the prevention or therapy of cardio-vascular complications like restenosis after percutaneous angioplasty or stenosis of venous bypasses, the graft versus host reaction, the ischemia/refusion-related damage in the context of surgical interventions and organ transplantation respectively, immunological hypersensitivity reactions, in particular the allergic rhinitis, the drug and food allergies, in particular urticaria and celiac disease (sprue), contact eczema and the immune complex diseases, in particular alveolitis, arthritis, glomerulonephritis and allergic vasculitis, inflammatory chondro- and osteopathies, in particular arthrosis, gout, ostitis and osteomyelitis, polyneuritis as well as acute and subacute respectively, infection contingent and in particular post-infectious inflammatory diseases, in particular bronchitis, endocarditis, hepatitis, myocarditis, nephritis, pericarditis, peritonitis and pancreatitis, including the septic shock.

    摘要翻译： 本发明涉及转录因子STAT-1的抑制剂，它们作为治疗方法的用途以及它们用于预防或治疗心血管并发症的用途，如经皮血管成形术或静脉旁路狭窄后的再狭窄，移植物抗宿主反应 ，外科手术和器官移植背景下的缺血/重塑相关损伤，免疫超敏反应，特别是过敏性鼻炎，药物和食物过敏症，特别是荨麻疹和乳糜泻（口腔），接触性湿疹和免疫 复杂疾病，特别是肺泡炎，关节炎，肾小球性肾炎和过敏性血管炎，炎性软骨和骨病，特别是关节病，痛风，口鼻炎和骨髓炎，多发性神经炎以及急性和亚急性感染，特别是感染后炎症性疾病， 特别是支气管炎，心内膜炎，肝炎，肌内 心包炎，肾炎，心包炎，腹膜炎和胰腺炎，包括败血性休克。