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公开(公告)号：US20130116171A1
公开(公告)日：2013-05-09
申请号：US13641451
申请日：2011-04-18
CPC分类号： A61K38/1825 , A61K9/0019 , A61K31/4439 , A61K45/06 , A61K47/60 , A61K47/61 , A61K2300/00
摘要： The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidaemia, obesity, and fatty liver.
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2.发明申请公开(公告)号：US20110263454A1
公开(公告)日：2011-10-27
申请号：US13061500
申请日：2009-08-28
申请人： Johan W. Jonker , Michael Downes , Ronald M. Evans
发明人： Johan W. Jonker , Michael Downes , Ronald M. Evans
CPC分类号： C12Q1/6897 , C12N15/1086
摘要： Provided herein is, inter alia, methods and compositions useful in therapeutic interrogation of complex physiologic pathways by massively parallel and permissive transcriptional screening. Thus, methods and compositions are provided herein that are useful for high-throughput functional analysis of complex, transcriptionally regulated physiological pathways. While examples are provided relating to nuclear receptors, the methods and composition can be generalized and applied to any class of transcription factor or any class of gene product that can regulate the activity of transcription. For example, in addition to nuclear receptors, the methods and compositions provided herein are generally applicable to all known transcription factors and any gene encoded product that modulates said transcription factor activity. Moreover, data obtained through the methods provided herein are directly comparable thereby facilitating high-throughput functional analysis.
摘要翻译： 本文提供了通过大规模平行和允许的转录筛选在治疗性询问复杂生理学途径中有用的方法和组合物。 因此，本文提供了可用于复杂的转录调节生理学途径的高通量功能分析的方法和组合物。 虽然提供了与核受体相关的实例，但是该方法和组成可以被推广并应用于可以调节转录活性的任何类型的转录因子或任何类型的基因产物。 例如，除了核受体之外，本文提供的方法和组合物通常可应用于调节所述转录因子活性的所有已知转录因子和任何基因编码产物。 此外，通过本文提供的方法获得的数据是直接可比的，因此有助于高通量功能分析。
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公开(公告)号：US09192601B2
公开(公告)日：2015-11-24
申请号：US12810123
申请日：2008-12-29
IPC分类号： A61K31/4178 , A61K31/426 , A61K31/47 , C12Q1/68
CPC分类号： A61K31/426 , A61K31/4178 , A61K31/47 , C12Q1/6876 , C12Q2600/136 , C12Q2600/158
摘要： Provided herein are methods and compositions for improving muscle performance and increasing endurance. Agonists of AMP-activated protein kinase (AMPK) and agonists of peroxisome proliferator-activated receptor delta (PPARδ) can be used in such treatments.
摘要翻译： 本文提供了用于改善肌肉性能和增加耐力的方法和组合物。 AMP活化蛋白激酶（AMPK）的激动剂和过氧化物酶体增殖物激活受体δ（PPARδ）的激动剂可用于此类治疗。
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4.发明申请公开(公告)号：US20110014126A1
公开(公告)日：2011-01-20
申请号：US12772981
申请日：2010-05-03
申请人： Ronald M. Evans , Michael Downes , Christopher Liddle , Nanthakumar Subramaniam , Caroline Flora Samer
发明人： Ronald M. Evans , Michael Downes , Christopher Liddle , Nanthakumar Subramaniam , Caroline Flora Samer
CPC分类号： A61K31/00 , A61K31/592 , A61K31/593 , G01N33/5067 , G01N33/82 , G01N2800/085
摘要： This application relates to methods of treating, preventing, and ameliorating fibrosis, such as fibrosis of the liver. In particular, the application relates to methods of using a vitamin D receptor agonist (such as vitamin D, vitamin D analogs, vitamin D precursors, and vitamin D receptor agonists precursors) for the treatment of liver fibrosis. Also disclosed are methods for screening for agents that treat, prevent, and ameliorate fibrosis.
摘要翻译： 本申请涉及治疗，预防和改善纤维化（例如肝纤维化）的方法。 特别地，本申请涉及使用维生素D受体激动剂（例如维生素D，维生素D类似物，维生素D前体和维生素D受体激动剂前体）用于治疗肝纤维化的方法。 还公开了用于筛选治疗，预防和改善纤维化的药剂的方法。
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公开(公告)号：US06673587B1
公开(公告)日：2004-01-06
申请号：US09637145
申请日：2000-08-11
IPC分类号： C12N916
CPC分类号： C12N9/16
摘要： The present invention relates to the identification, isolation, sequencing and characterization of a new member of the histone deacetylase family, as well as its transcripts, gene products, associated sequence information, and related genes. The present invention also relates to methods for detecting and diagnosing carriers of normal and mutant alleles of these genes, methods for detecting and diagnosing diseases, methods of identifying genes and proteins related to or interacting with such genes and proteins, methods of screening for potential therapeutics for diseases, methods of treatment for diseases, and to cell lines and animal models useful in screening for and evaluating potentially useful therapies for diseases. In a particular aspect of the present invention, a novel family member, HDAC7, is described and its interaction with SMRT/N-CoR and mSin3A, its biochemical properties and subcellular localization are characterized. In addition, evidence is provided that the HDAC4, 5, and 7 deacetylases may mediate nuclear receptor repression. The findings described here indicate that two or more classes of histone deacetylases can collectively contribute to SMRT/N-CoR action and that at least some deacetylases may directly associate with SMRT/N-CoR in a mSin3A independent fashion.
摘要翻译： 本发明涉及组蛋白脱乙酰酶家族的新成员以及其转录物，基因产物，相关序列信息和相关基因的鉴定，分离，测序和表征。 本发明还涉及用于检测和诊断这些基因的正常和突变等位基因的载体的方法，用于检测和诊断疾病的方法，鉴定与这些基因和蛋白质相关或与之相互作用的基因和蛋白质的方法，筛选潜在治疗剂的方法 用于疾病的治疗方法，以及用于筛选和评估潜在有用的疾病疗法的细胞系和动物模型。 在本发明的特定方面，描述了新型家族成员HDAC7，并且与SMRT / N-CoR和mSin3A的相互作用，其生物化学性质和亚细胞定位被表征。 此外，证据表明HDAC4,5和7脱乙酰酶可能介导核受体抑制。 这里描述的发现表明，两种或更多类组蛋白脱乙酰酶可以共同促进SMRT / N-CoR作用，并且至少一些脱乙酰酶可以以独立于mSin3A的方式直接与SMRT / N-CoR相关联。
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6.发明授权Modulation of estrogen receptor-related receptor gamma (ERRγ) and uses therefor 有权调节雌激素受体相关受体γ（ERRγ）及其用途公开(公告)号：US08962546B2
公开(公告)日：2015-02-24
申请号：US13410142
申请日：2012-03-01
申请人： Vihang A. Narkar , Michael Downes , Ruth T. Yu , Ronald M. Evans
发明人： Vihang A. Narkar , Michael Downes , Ruth T. Yu , Ronald M. Evans
CPC分类号： A61K38/1796 , A61K31/166 , A61K31/381 , A61K31/655 , A61K38/177 , A61K48/00 , A61K48/005 , A61K48/0058 , A61K48/0066
摘要： This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERRγ activity to the subject. Such agents can include one or more ERRγ agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).
摘要翻译： 本申请提供了通过施用治疗有效量的一种或多种增加对受试者的ERRγ活性的药物来增加血管形成，肌肉功能，肌肉恢复和/或线粒体活性的方法。 这样的试剂可以包括一种或多种ERRγ激动剂。 在一些例子中，该方法不要求主体锻炼，因此主体可能是久坐的（如卧床不起或在轮椅上）。
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7.发明授权Use of vitamin D receptor agonists, ligands, and precursors to treat pancreatic fibrosis 有权使用维生素D受体激动剂，配体和前体来治疗胰腺纤维化公开(公告)号：US08318708B2
公开(公告)日：2012-11-27
申请号：US12772981
申请日：2010-05-03
申请人： Ronald M. Evans , Michael Downes , Christopher Liddle , Nanthakumar Subramaniam , Caroline Flora Samer
发明人： Ronald M. Evans , Michael Downes , Christopher Liddle , Nanthakumar Subramaniam , Caroline Flora Samer
IPC分类号： A61K31/59 , A61K31/592 , A61K31/593
CPC分类号： A61K31/00 , A61K31/592 , A61K31/593 , G01N33/5067 , G01N33/82 , G01N2800/085
摘要： This application relates to methods of treating and ameliorating fibrosis, such as fibrosis of the pancreas. In particular, the application relates to methods of using a vitamin D receptor agonist (such as vitamin D, vitamin D analogs, vitamin D precursors, and vitamin D receptor agonists precursors) for the treatment of pancreatic fibrosis.
摘要翻译： 本申请涉及治疗和改善纤维化的方法，如胰腺纤维化。 特别地，本申请涉及使用维生素D受体激动剂（例如维生素D，维生素D类似物，维生素D前体和维生素D受体激动剂前体）用于治疗胰腺纤维化的方法。
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公开(公告)号：US20080187928A1
公开(公告)日：2008-08-07
申请号：US11966851
申请日：2007-12-28
申请人： Ronald M. Evans , Vihang A. Narkar , Yong-Xu Wang , Michael Downes , Ruth T. Yu
发明人： Ronald M. Evans , Vihang A. Narkar , Yong-Xu Wang , Michael Downes , Ruth T. Yu
CPC分类号： A61K31/426 , A61K31/4178 , A61K31/47 , C12Q1/6876 , C12Q2600/124 , C12Q2600/136 , C12Q2600/158
摘要： Disclosed herein are methods for enhancing one or more effects of exercise in a subject by administering a PPARδ agonist (e.g., GW1516) to the subject in combination with an exercise program. Also disclosed are gene expression profiles unique to the combination of agonist-induced PPARδ activation and exercise. Such profiles are useful, at least, in methods for identifying the use of performance-enhancing drugs in exercised subjects (such as, professional or athletes). Direct interactions between PPARδ and exercised-induced kinases (e.g., AMPK or its subunits, AMPK α1 and/or AMPK α2) also are disclosed. Such protein-protein interactions provide new targets for identification of useful compounds.
摘要翻译： 本文公开了通过与运动程序结合施用PPARδ激动剂（例如，GW1516）来增强受试者的运动的一种或多种作用的方法。 还公开了激动剂诱导的PPARδ激活和运动的组合独特的基因表达谱。 至少在确定在锻炼对象（如专业人员或运动员）中使用性能增强药物的方法中，这种概况很有用。 PPARδ与锻炼诱导的激酶（例如AMPK或其亚基，AMPKα1和/或AMPKα2）之间的直接相互作用也被公开。 这种蛋白质 - 蛋白质相互作用提供了鉴定有用化合物的新靶标。
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9.发明申请MODULATION OF ESTROGEN RECEPTOR-RELATED RECEPTOR GAMMA (ERR GAMMA) AND USES THEREFOR 有权雌激素受体相关受体GAMMA（ERR GAMMA）的调节及其用途公开(公告)号：US20120302491A1
公开(公告)日：2012-11-29
申请号：US13410142
申请日：2012-03-01
申请人： Vihang A. Narkar , Michael Downes , Ruth T. Yu , Ronald M. Evans
发明人： Vihang A. Narkar , Michael Downes , Ruth T. Yu , Ronald M. Evans
CPC分类号： A61K38/1796 , A61K31/166 , A61K31/381 , A61K31/655 , A61K38/177 , A61K48/00 , A61K48/005 , A61K48/0058 , A61K48/0066
摘要： This application provides methods of increasing vascularization, muscle performance, muscle rehabilitation, and/or mitochondrial activity in subjects in need thereof, by administering a therapeutically effective amount of one or more agents that increases ERRγ activity to the subject. Such agents can include one or more ERRγ agonists. In some examples the method does not require that the subject exercise, and as such, the subject may be sedentary (such as bedridden or in a wheelchair).
摘要翻译： 本申请提供了通过施用治疗有效量的一种或多种增加对受试者的ERRγ活性的药物来增加血管形成，肌肉功能，肌肉恢复和/或线粒体活性的方法。 这样的试剂可以包括一种或多种ERRγ激动剂。 在一些例子中，该方法不要求主体锻炼，因此主体可能是久坐的（如卧床不起或在轮椅上）。
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公开(公告)号：US20110112047A1
公开(公告)日：2011-05-12
申请号：US12810123
申请日：2008-12-29
IPC分类号： A61K31/7056 , A61P21/06 , A61P3/04 , C40B30/04
CPC分类号： A61K31/426 , A61K31/4178 , A61K31/47 , C12Q1/6876 , C12Q2600/136 , C12Q2600/158
摘要： This disclosure concerns the use of agonists of AMP-activated protein kinase (AMPK) for improving exercise and modifying energy metabolism in a subject. The disclosure also relates to a combination of AMPK and peroxisome proliferator-activated receptor (PPAR) δ agonists for improving exercise performance in a subject, methods for identifying substance-enhanced exercise performance in a subject, and methods for identifying compounds that affect the interaction of PPARδ with exercise-induced kinases.
摘要翻译： 本公开涉及AMP激活蛋白激酶（AMPK）的激动剂用于改善受试者的运动和改变能量代谢的用途。 本公开还涉及用于改善受试者的运动性能的AMPK和过氧化物酶体增殖物激活受体（PPAR）δ激动剂的组合，用于鉴定受试者中物质增强的运动性能的方法，以及用于鉴定影响受试者的相互作用的化合物的方法 PPARδ与运动诱发的激酶。
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