知搜-全球专利检索

  1. 登录
  2. 注册

搜索结果

17 条记录 (耗时 0.025 秒)

    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis
    3.
    发明授权
    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis 有权
    用于治疗层状病毒，细胞衰老和动脉粥样硬化的法呢基转移酶抑制剂

    公开(公告)号：US07838531B2

    公开(公告)日：2010-11-23

    申请号：US11828117

    申请日：2007-07-25

    申请人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    发明人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    IPC分类号： A61K49/00 ,  A61K31/445 ,  C12Q1/48 ,  A01N43/42

    CPC分类号： A61K31/4545 ,  A61K31/4709 ,  A61K45/06 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/68 ,  G01N2333/91171 ,  G01N2500/04 ,  G01N2500/10

    摘要： Although it can be farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.

    摘要翻译： 虽然它可以被法呢基化，但是在和记吉尔福德综合症（Hutchison Gilford Progeria Syndrome，HGPS）中表达的突变体蛋白A蛋白不能被脱甲酰化，因为特征性突变导致结合蛋白酶ZMPSTE24所必需的切割位点的缺失并进行脱甲基化。 结果是异常的法呢基蛋白（称为“progerin”），其改变正常的lamin A功能作为显性阴性，并且通过与核膜的结合来假设其自身的异常功能。 法呢基化的保留，以及progerin和其他异常的lamin基因蛋白产物的潜在的其他异常性质产生疾病。 法尼基转移酶抑制剂（FTIs）（直接作用剂和间接抑制剂）将抑制progerin的形成，导致lamin A蛋白的降低和/或增加的prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样，FTIs治疗应改善progeria和其他层层病的疾病状况。 此外，在用法呢基转移酶抑制剂治疗后，动脉粥样硬化和非层状病变个体的老化将会改善。

    LMNA gene and its involvement in Hutchinson-Gilford Progeria Syndrome (HGPS) and arteriosclerosis
    4.
    发明授权
    LMNA gene and its involvement in Hutchinson-Gilford Progeria Syndrome (HGPS) and arteriosclerosis 有权
    LMNA基因及其参与Hutchinson-Gilford Progeria综合征（HGPS）和动脉硬化

    公开(公告)号：US07297492B2

    公开(公告)日：2007-11-20

    申请号：US10943400

    申请日：2004-09-17

    申请人： B. Maria H. Eriksson ,  Francis S. Collins ,  Leslie B. Gordon ,  W. Ted Brown

    发明人： B. Maria H. Eriksson ,  Francis S. Collins ,  Leslie B. Gordon ,  W. Ted Brown

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N2500/04 ,  Y10T436/143333

    摘要： Disclosed herein are point mutations in the LMNA gene that cause HGPS. These mutations activate a cryptic splice site within the LMNA gene, which leads to deletion of part of exon 11 and generation of a mutant Lamin A protein product that is 50 amino acids shorter than the normal protein. In addition to the novel Lamin A variant protein and nucleic acids encoding this variant, methods of using these molecules in detecting biological conditions associated with a LMNA mutation in a subject (e.g., HGPS, arteriosclerosis, and other age-related diseases), methods of treating such conditions, methods of selecting treatments, methods of screening for compounds that influence Lamin A activity, and methods of influencing the expression of LMNA or LMNA variants are also described. Oligonucleotides and other compounds for use in examples of the described methods are also provided, as are protein-specific binding agents, such as antibodies, that bind specifically to at least one epitope of a Lamin A variant protein preferentially compared to wildtype Lamin A, and methods of using such antibodies in diagnosis, treatment, and screening. Also provided are kits for carrying out the methods described herein.

    摘要翻译： 本文公开了导致HGPS的LMNA基因中的点突变。 这些突变激活LMNA基因内的隐性剪接位点，导致部分外显子11的缺失和产生比正常蛋白短50个氨基酸的突变Lamin A蛋白产物。 除了新型Lamin A变体蛋白和编码该变体的核酸之外，使用这些分子检测与受试者的LMNA突变相关的生物学条件（例如，HGPS，动脉硬化和其他与年龄相关的疾病）的方法， 还描述了治疗这些病症，选择治疗方法，筛选影响Lamin A活性的化合物的方法，以及影响LMNA或LMNA变体表达的方法。 还提供了用于所述方法的实施例的寡核苷酸和其它化合物，以及优选与野生型Lamin A相比特异性结合Lamin A变体蛋白的至少一个表位的蛋白质特异性结合剂，例如抗体，以及 在诊断，治疗和筛查中使用这些抗体的方法。 还提供了用于实施本文所述方法的试剂盒。

    FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS
    6.
    发明申请
    FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS 失效
    用于治疗肌肉瘤，细胞衰老和甲状腺功能亢进症的纤维素酶抑制剂

    公开(公告)号：US20120329066A1

    公开(公告)日：2012-12-27

    申请号：US13567432

    申请日：2012-08-06

    申请人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    发明人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    IPC分类号： C12Q1/68

    CPC分类号： A61K31/4545 ,  A61K31/4709 ,  A61K45/06 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/68 ,  G01N2333/91171 ,  G01N2500/04 ,  G01N2500/10

    摘要： Although it can be farnesylated, mutant lamin A expressed in Hutchinson Gilford Progeria Syndrome cannot be defarnesylated; the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (“progerin”) that alters normal lamin A function as a dominant negative, and assumes its own aberrant function through its association with the nuclear membrane. Retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) will inhibit formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with FTIs.

    摘要翻译： 虽然它可以被法呢基化，但在Hutchinson Gilford Progeria综合征中表达的突变体蛋白A不能被脱乙酰化; 特征突变导致结合蛋白酶ZMPSTE24所需的切割位点的缺失并进行脱甲酰化。 结果是异常的法呢基蛋白（progerin），其改变正常的lamin A功能作为显性阴性，并且通过与核膜的相关性而呈现其自身的异常功能。 法尼基化的保留，以及progerin和其他异常的lamin基因蛋白产物的潜在其他异常性质产生疾病。 法呢基转移酶抑制剂（FTIs）将抑制progerin的形成，导致lamin A蛋白降低，和/或增加prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样，FTIs治疗应改善progeria和其他层层病的疾病状况。 此外，FTIs治疗后，动脉粥样硬化和非层状病变个体的老化因素将有所改善。

    FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS
    7.
    发明申请
    FARNESYLTRANSFERASE INHIBITORS FOR TREATMENT OF LAMINOPATHIES, CELLULAR AGING AND ATHEROSCLEROSIS 有权
    用于治疗肌肉瘤，细胞衰老和甲状腺功能亢进症的纤维素酶抑制剂

    公开(公告)号：US20080131375A1

    公开(公告)日：2008-06-05

    申请号：US11828117

    申请日：2007-07-25

    申请人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    发明人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    IPC分类号： A61K49/00 ,  A61K31/4709 ,  A61P43/00 ,  A61K31/4545

    CPC分类号： A61K31/4545 ,  A61K31/4709 ,  A61K45/06 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/68 ,  G01N2333/91171 ,  G01N2500/04 ,  G01N2500/10

    摘要： Although it can be farnesylated, the mutant lamin A protein expressed in Hutchison Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.

    摘要翻译： 虽然它可以被法呢基化，但是在和记吉尔福德综合症（Hutchison Gilford Progeria Syndrome，HGPS）中表达的突变体蛋白A蛋白不能被脱甲酰化，因为特征性突变导致结合蛋白酶ZMPSTE24所必需的切割位点的缺失并进行脱甲基化。 结果是异常的法呢基蛋白（称为“progerin”），其改变正常的lamin A功能作为显性阴性，并且通过与核膜的结合来假设其自身的异常功能。 法呢基化的保留，以及progerin和其他异常的lamin基因蛋白产物的潜在的其他异常性质产生疾病。 法尼基转移酶抑制剂（FTIs）（直接作用剂和间接抑制剂）将抑制progerin的形成，导致lamin A蛋白的降低和/或增加的prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样，FTIs治疗应改善progeria和其他层层病的疾病状况。 此外，在用法呢基转移酶抑制剂治疗后，动脉粥样硬化和非层状病变个体的老化将会改善。

    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis
    9.
    发明授权
    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis 失效
    用于治疗层状病毒，细胞衰老和动脉粥样硬化的法呢基转移酶抑制剂

    公开(公告)号：US08691501B2

    公开(公告)日：2014-04-08

    申请号：US13567432

    申请日：2012-08-06

    申请人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    发明人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    IPC分类号： C12Q1/00 ,  C12Q1/02

    CPC分类号： A61K31/4545 ,  A61K31/4709 ,  A61K45/06 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/68 ,  G01N2333/91171 ,  G01N2500/04 ,  G01N2500/10

    摘要： Although it can be farnesylated, mutant lamin A expressed in Hutchinson Gilford Progeria Syndrome cannot be defarnesylated; the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (“progerin”) that alters normal lamin A function as a dominant negative, and assumes its own aberrant function through its association with the nuclear membrane. Retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) will inhibit formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with FTIs.

    摘要翻译： 虽然它可以被法呢基化，但在Hutchinson Gilford Progeria综合征中表达的突变体蛋白A不能被脱乙酰化; 特征突变导致结合蛋白酶ZMPSTE24所需的切割位点的缺失并进行脱甲酰化。 结果是异常的法呢基蛋白（“progerin”），其改变正常的层叠A功能作为显性阴性，并且通过与核膜的结合而呈现其自身的异常功能。 法尼基化的保留，以及progerin和其他异常的lamin基因蛋白产物的潜在其他异常性质产生疾病。 法呢基转移酶抑制剂（FTIs）将抑制progerin的形成，导致lamin A蛋白降低，和/或增加prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样，FTIs治疗应改善progeria和其他层层病的疾病状况。 此外，FTIs治疗后，动脉粥样硬化和非层状病变个体的老化因素将有所改善。

    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis
    10.
    发明授权
    Farnesyltransferase inhibitors for treatment of laminopathies, cellular aging and atherosclerosis 失效
    用于治疗层状病毒，细胞衰老和动脉粥样硬化的法呢基转移酶抑制剂

    公开(公告)号：US08257915B2

    公开(公告)日：2012-09-04

    申请号：US12905838

    申请日：2010-10-15

    申请人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    发明人： Leslie B. Gordon ,  Francis S. Collins ,  Thomas Glover ,  Michael W. Glynn ,  Brian C. Capell ,  Adrienne D. Cox ,  Channing J. Der

    IPC分类号： C12Q1/00 ,  C12Q1/02

    CPC分类号： A61K31/4545 ,  A61K31/4709 ,  A61K45/06 ,  C07K14/47 ,  C12Q1/6883 ,  C12Q1/6886 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/68 ,  G01N2333/91171 ,  G01N2500/04 ,  G01N2500/10

    摘要： Although it can be farnesylated, the mutant lamin A protein expressed in Hutchinson Gilford Progeria Syndrome (HGPS) cannot be defarnesylated because the characteristic mutation causes deletion of a cleavage site necessary for binding the protease ZMPSTE24 and effecting defarnesylation. The result is an aberrant farnesylated protein (called “progerin”) that alters normal lamin A function as a dominant negative, as well as assuming its own aberrant function through its association with the nuclear membrane. The retention of farnesylation, and potentially other abnormal properties of progerin and other abnormal lamin gene protein products, produces disease. Farnesyltransferase inhibitors (FTIs) (both direct effectors and indirect inhibitors) will inhibit the formation of progerin, cause a decrease in lamin A protein, and/or an increase prelamin A protein. Decreasing the amount of aberrant protein improves cellular effects caused by and progerin expression. Similarly, treatment with FTIs should improve disease status in progeria and other laminopathies. In addition, elements of atherosclerosis and aging in non-laminopathy individuals will improve after treatment with farnesyltransferase inhibitors.

    摘要翻译： 虽然它可以被法呢基化，但是在Hutchinson Gilford Progeria综合征（HGPS）中表达的突变体蛋白A蛋白质不能被脱甲酰化，因为特征性突变导致缺失结合蛋白酶ZMPSTE24所必需的切割位点并进行脱甲酰化。 结果是异常的法呢基蛋白（称为“progerin”），其改变正常的lamin A功能作为显性阴性，并且通过与核膜的结合来假设其自身的异常功能。 法呢基化的保留，以及progerin和其他异常的lamin基因蛋白产物的潜在的其他异常性质产生疾病。 法尼基转移酶抑制剂（FTIs）（直接作用剂和间接抑制剂）将抑制progerin的形成，导致lamin A蛋白的降低和/或增加的prelamin A蛋白。 减少异常蛋白质的量会改善由progerin表达引起的细胞效应。 同样，FTIs治疗应改善progeria和其他层层病的疾病状况。 此外，在用法呢基转移酶抑制剂治疗后，动脉粥样硬化和非层状病变个体的老化将会改善。