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    Inhibitors of the BMP signaling pathway
    1.
    发明授权
    Inhibitors of the BMP signaling pathway 有权
    BMP信号通路抑制剂

    公开(公告)号：US09045484B2

    公开(公告)日：2015-06-02

    申请号：US13940641

    申请日：2013-07-12

    申请人： The Brigham and Women's Hospital, Inc. ,  The General Hospital Corporation

    发明人： Paul B. Yu ,  Gregory D. Cuny ,  Kenneth D. Bloch ,  Randall T. Peterson ,  Charles C. Hong

    IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  C07D487/04

    CPC分类号： C07D487/04 ,  A61K31/519

    摘要： The present invention provides pyridinyl-substituted pyrazolyl pyrimidine small molecule inhibitors of bone morphogenetic protein (BMP) signaling having the structure of formula (I), wherein variables A, B, E, F, X, Y, Z, Ar, L1, R4 and R15 are as defined in the specification. The compounds of the invention are useful in modulating cell growth, differentiation, proliferation, and apoptosis, and thus are useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

    摘要翻译： 本发明提供具有式（I）结构的吡啶基取代的吡唑基嘧啶小分子抑制剂骨形态发生蛋白（BMP）信号转导酶，其中变量A，B，E，F，X，Y，Z，Ar，L1，R4 和R 15如说明书中所定义。 本发明的化合物可用于调节细胞生长，分化，增殖和凋亡，因此可用于治疗与BMP信号相关的疾病或病症，包括炎症，心血管疾病，血液病，癌症和骨骼疾病 用于调节细胞分化和/或增殖。

    BMP INHIBITORS AND METHODS OF USE THEREOF
    2.
    发明申请
    BMP INHIBITORS AND METHODS OF USE THEREOF 审中-公开
    BMP抑制剂及其使用方法

    公开(公告)号：US20160115167A1

    公开(公告)日：2016-04-28

    申请号：US14772630

    申请日：2014-03-04

    申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ,  THE GENERAL HOSPITAL CORPORATION

    发明人： Paul B. Yu ,  Gregory D. Cuny ,  Agustin H. Mohedas ,  Kenneth D. Bloch ,  Randall T. Peterson

    IPC分类号： C07D487/04

    CPC分类号： C07D487/04

    摘要： The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation. These compounds may also be used to reduce circulating levels of ApoB-100 or LDL and treat or prevent acquired or congenital hypercholesterolemia or hyperlipoproteinemia; diseases, disorders, or syndromes associated with defects in lipid absorption or metabolism; or diseases, disorders, or syndromes caused by hyperlipidemia.

    摘要翻译： 本发明提供BMP信号传导的小分子抑制剂。 这些化合物可用于调节细胞生长，分化，增殖和凋亡，因此可用于治疗与BMP信号相关的疾病或病症，包括炎症，心血管疾病，血液病，癌症和骨骼疾病，以及 用于调节细胞分化和/或增殖。 这些化合物也可用于降低ApoB-100或LDL的循环水平，并治疗或预防获得性或先天性高胆固醇血症或高脂蛋白血症; 与脂质吸收或代谢缺陷相关的疾病，病症或综合征; 或由高脂血症引起的疾病，病症或综合征。

    INHIBITORS OF THE BMP SIGNALING PATHWAY
    3.
    发明申请
    INHIBITORS OF THE BMP SIGNALING PATHWAY 有权
    BMP信号通路的抑制剂

    公开(公告)号：US20140011805A1

    公开(公告)日：2014-01-09

    申请号：US13940641

    申请日：2013-07-12

    申请人： The General Hospital Corporation ,  The Brigham and Women's Hospital, Inc.

    发明人： Paul B. Yu ,  Gregory D. Cuny ,  Kenneth D. Bloch ,  Randall T. Peterson ,  Charles C. Hong

    IPC分类号： C07D487/04

    CPC分类号： C07D487/04 ,  A61K31/519

    摘要： The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.

    摘要翻译： 本发明提供BMP信号传导的小分子抑制剂。 这些化合物可用于调节细胞生长，分化，增殖和凋亡，因此可用于治疗与BMP信号相关的疾病或病症，包括炎症，心血管疾病，血液病，癌症和骨骼疾病，以及 用于调节细胞分化和/或增殖。

    Inhibitors of microRNAs that regulate production of atrial natriuretic peptide (ANP) as therapeutics and uses thereof
    6.
    发明授权
    Inhibitors of microRNAs that regulate production of atrial natriuretic peptide (ANP) as therapeutics and uses thereof 有权
    调节心房钠尿肽（ANP）生产的微小RNA的抑制剂作为治疗剂及其用途

    公开(公告)号：US09388412B2

    公开(公告)日：2016-07-12

    申请号：US14408189

    申请日：2013-06-14

    申请人： THE GENERAL HOSPITAL CORPORATION

    发明人： Kenneth D. Bloch ,  Pankaj Arora ,  Christopher Newton-Cheh ,  Thomas J. Wang

    IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  C12N15/11 ,  C12Q1/68 ,  A61K31/7088 ,  A61K45/06

    CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/00 ,  C12N15/111 ,  C12N2310/113 ,  C12N2320/31 ,  C12N2320/34 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/178

    摘要： The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject. Other aspects of the present invention relates to assays, methods and systems to identify a subject at risk of hypertension, or identifying a subject suitable to administration of an anti-miR-425 agent for treatment of hypertension, the assay comprising assessing if a subject is homozygous or heterozygous for the major (A) allele of rs5068 SNP, and/or assaying for levels of miR-425 and/or assaying for levels of NT-proANP and/or levels of ANP in the plasma of a subject.

    摘要翻译： 本发明涉及用于治疗受试者中的高血压和其它心血管疾病的方法，试剂盒和组合物，特别是治疗或预防受试者心血管疾病的方法，包括向受试者施用至少一种抗miR剂至miRNA -425。 在一些实施方案中，抗miR剂是与SEQ ID NO：1的至少一部分miR-425互补的小分子或寡核苷酸，或与至少部分miRNA种子序列AUGACA互补的抗miR SEQ ID NO：2）。 本发明的另一方面涉及治疗受试者的低血压的方法，试剂盒和组合物，其包括施用包含miR-425试剂的组合物以降低受试者的ANP水平。 本发明的其它方面涉及用于鉴定患有高血压危险的受试者或鉴定适合于施用抗miR-425药物以治疗高血压的受试者的测定，方法和系统，所述测定包括评估受试者是否为 对于rs5068 SNP的主要（A）等位基因，和/或测定miR-425的水平和/或测定受试者血浆中NT-proANP水平和/或ANP水平的纯合或杂合。

    INHIBITORS OF MICRORNAs THAT REGULATE PRODUCTION OF ATRIAL NATRIURETIC PEPTIDE (ANP) AS THERAPEUTICS AND USES THEREOF
    8.
    发明申请
    INHIBITORS OF MICRORNAs THAT REGULATE PRODUCTION OF ATRIAL NATRIURETIC PEPTIDE (ANP) AS THERAPEUTICS AND USES THEREOF 有权
    调节作为治疗剂的ATRIAL NATRIURETIC PEPTIDE（ANP）生产的微生物抑制剂及其用途

    公开(公告)号：US20150133521A1

    公开(公告)日：2015-05-14

    申请号：US14408189

    申请日：2013-06-14

    申请人： THE GENERAL HOSPITAL CORPORATION

    发明人： Kenneth D. Bloch ,  Pankaj Arora ,  Christopher Newton-Cheh ,  Thomas J. Wang

    IPC分类号： C12N15/113 ,  A61K45/06 ,  C12Q1/68 ,  A61K31/7088

    CPC分类号： C12N15/113 ,  A61K31/7088 ,  A61K45/06 ,  A61K48/00 ,  C12N15/111 ,  C12N2310/113 ,  C12N2320/31 ,  C12N2320/34 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/156 ,  C12Q2600/178

    摘要： The present invention relates to methods, kits and compositions to treat hypertension and other cardiovascular diseases in a subject, in particular, a method of treating or preventing a cardiovascular disease in a subject comprising administering to a subject at least one anti-miR agent to miRNA-425. In some embodiments, an anti-miR agent is a small molecule or an oligonucleotide complementary to at least part of the miR-425 of SEQ ID NO: 1, or an anti-miR complementary to at least part of the miRNA seed sequence AUGACA (SEQ ID NO: 2). Another aspect of the present invention relates to methods, kits and compositions to treat low blood pressure in a subject comprising administering a composition comprising a miR-425 agent to decrease ANP levels in the subject. Other aspects of the present invention relates to assays, methods and systems to identify a subject at risk of hypertension, or identifying a subject suitable to administration of an anti-miR-425 agent for treatment of hypertension, the assay comprising assessing if a subject is homozygous or heterozygous for the major (A) allele of rs5068 SNP, and/or assaying for levels of miR-425 and/or assaying for levels of NT-proANP and/or levels of ANP in the plasma of a subject.

    摘要翻译： 本发明涉及用于治疗受试者中的高血压和其它心血管疾病的方法，试剂盒和组合物，特别是治疗或预防受试者心血管疾病的方法，包括向受试者施用至少一种抗miR剂至miRNA -425。 在一些实施方案中，抗miR剂是与SEQ ID NO：1的至少一部分miR-425互补的小分子或寡核苷酸，或与至少部分miRNA种子序列AUGACA互补的抗miR SEQ ID NO：2）。 本发明的另一方面涉及治疗受试者的低血压的方法，试剂盒和组合物，其包括施用包含miR-425试剂的组合物以降低受试者的ANP水平。 本发明的其它方面涉及用于鉴定患有高血压危险的受试者或鉴定适于施用抗miR-425药物以治疗高血压的受试者的测定，方法和系统，所述测定包括评估受试者是否为 对于rs5068 SNP的主要（A）等位基因，和/或测定miR-425的水平和/或测定受试者血浆中NT-proANP水平和/或ANP水平的纯合或杂合。