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公开(公告)号：US20100105036A1
公开(公告)日：2010-04-29
申请号：US12408575
申请日：2009-03-20
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
摘要翻译： 本发明涉及通过修饰SIR2和/或转录因子活性（例如p53）来筛选调节细胞和生物体过程的化合物的方法，特别是筛选修饰细胞或生物体的寿命和/或代谢的化合物的方法 通过调节SIR2和/或转录因子例如p53的活性，更具体地涉及筛选调节Sir2和/或转录因子例如p53的活性的化合物的方法。 特别地，本发明涉及通过提供包含转录因子Sir2和Sir2辅因子与该化合物的测试混合物来筛选化合物的方法，并且在存在下评价测试混合物的组分的活性 化合物。 本发明还涉及所述化合物的治疗用途。 本发明还涉及通过提高Sir2的局部浓度来改变组蛋白或DNA上的转录因子结合位点的乙酰化状态的方法。
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公开(公告)号：US20060252076A1
公开(公告)日：2006-11-09
申请号：US11404146
申请日：2006-04-13
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
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公开(公告)号：US20130071378A1
公开(公告)日：2013-03-21
申请号：US13523412
申请日：2012-06-14
IPC分类号： C12Q1/68
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： Methods for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound are described.
摘要翻译： 描述了通过向化合物提供包含转录因子Sir2和Sir2辅因子的测试混合物并在化合物存在下评价测试混合物的组分的活性来筛选化合物的方法。
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公开(公告)号：US07572575B2
公开(公告)日：2009-08-11
申请号：US11404146
申请日：2006-04-13
IPC分类号： C12Q1/00 , G01N33/53 , G01N33/567
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： This invention relates to methods of screening compounds that modulate cellular and organismal processes by modification of the activity of SIR2 and/or transcription factors, e.g., p53, particularly methods of screening for compounds that modify lifespan and/or metabolism of a cell or an organism by modulation of the activity of SIR2 and/or transcription factors, e.g., p53, and more particularly to methods of screening for compounds that modulate the activity of Sir2 and/or transcription factors, e.g., p53. In particular, the present invention relates to a method for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound. The invention further relates to therapeutic uses of said compounds. The invention further relates to a method of modifying the acetylation status of a transcription factor binding site on histone or DNA by raising local concentrations of Sir2.
摘要翻译： 本发明涉及通过修饰SIR2和/或转录因子（例如p53）的活性来调节细胞和生物体过程的化合物的方法，特别是筛选修饰细胞或生物体的寿命和/或代谢的化合物的方法 通过调节SIR2和/或转录因子例如p53的活性，更具体地涉及筛选调节Sir2和/或转录因子例如p53的活性的化合物的方法。 特别地，本发明涉及通过提供包含转录因子Sir2和Sir2辅因子与该化合物的测试混合物来筛选化合物的方法，并且在存在下评价测试混合物的组分的活性 化合物。 本发明还涉及所述化合物的治疗用途。 本发明还涉及通过提高Sir2的局部浓度来改变组蛋白或DNA上的转录因子结合位点的乙酰化状态的方法。
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公开(公告)号：US08546074B2
公开(公告)日：2013-10-01
申请号：US13523412
申请日：2012-06-14
IPC分类号： C12Q1/00 , G01N33/53 , G01N33/567
CPC分类号： C12Q1/68 , C12Q1/44 , G01N2333/4703 , G01N2333/916 , G01N2500/02
摘要： Methods for screening a compound, by providing a test mixture comprising a transcription factor, Sir2, and a Sir2 cofactor with the compound, and evaluating an activity of a component of the test mixture in the presence of the compound are described.
摘要翻译： 描述了通过向化合物提供包含转录因子Sir2和Sir2辅因子的测试混合物并在化合物存在下评价测试混合物的组分的活性来筛选化合物的方法。
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6.发明授权Methods for identifying agents that alter NAD-dependent deacetylation activity of a SIR2 protein 有权用于鉴定改变SIR2蛋白的NAD依赖性脱乙酰活性的试剂的方法公开(公告)号：US08642284B1
公开(公告)日：2014-02-04
申请号：US09735786
申请日：2000-12-13
CPC分类号： C12Q1/48 , G01N2333/98 , G01N2440/10 , G01N2500/00
摘要： Methods of identifying agents which alter the NAD-dependent deacetylation activity of a Sir2 protein or a fragment of a Sir2 protein are disclosed. The acetylated protein can be a nuclear protein, such as a histone protein, or a cytoplasmic protein. The Sir2 protein employed in the methods can include at least a core domain of a Sir2 protein, such as a human Sir2 protein.
摘要翻译： 公开了鉴定改变Sir2蛋白或Sir2蛋白片段的NAD依赖性脱乙酰活性的试剂的方法。 乙酰化蛋白可以是核蛋白，例如组蛋白，或细胞质蛋白。 用于该方法的Sir2蛋白质可以包括Sir2蛋白质的至少核心结构域，例如人Sir2蛋白质。
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公开(公告)号：US08268575B2
公开(公告)日：2012-09-18
申请号：US11575605
申请日：2005-09-20
IPC分类号： C12P19/36 , C07H21/04 , G01N33/573 , C12N15/63 , C12N5/10
CPC分类号： C12P19/36 , C12N9/1077
摘要： The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.
摘要翻译： 本发明一般涉及烟酰胺腺嘌呤二核苷酸（NAD）生物合成系统和筛选NAD生物合成效应物的方法。 在本发明的各个方面中，提供体外重构的哺乳动物NAD生物合成系统，其可用于化学活化剂的高通量筛选和用于哺乳动物NAD生物合成的抑制剂。 本发明的另一方面提供了鉴定影响NAD代谢酶的体内活性的化合物的方法。 本发明的其它方面包括可用于本文所述方法的核酸序列，载体和转化的细胞。
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公开(公告)号：US20090246803A1
公开(公告)日：2009-10-01
申请号：US11575605
申请日：2005-09-20
CPC分类号： C12P19/36 , C12N9/1077
摘要： The present invention generally relates to a nicotinamide adenine dinucleotide (NAD) biosynthesis system and methods of screening for NAD biosynthesis effectors. Among the various aspects of the present invention is the provision of an in vitro-reconstituted mammalian NAD biosynthesis system that can be used for the high-throughput screening of chemical activators and inhibitors for mammalian NAD biosynthesis. Another aspect of the invention provides a method of identifying a compound that effects in vivo activity of NAD metabolic enzymes. Further aspects of the invention include nucleic acid sequences, vectors, and transformed cells that can be used in the methods described herein.
摘要翻译： 本发明一般涉及烟酰胺腺嘌呤二核苷酸（NAD）生物合成系统和筛选NAD生物合成效应物的方法。 在本发明的各个方面中，提供体外重构的哺乳动物NAD生物合成系统，其可用于化学活化剂的高通量筛选和用于哺乳动物NAD生物合成的抑制剂。 本发明的另一方面提供了鉴定影响NAD代谢酶的体内活性的化合物的方法。 本发明的其它方面包括可用于本文所述方法的核酸序列，载体和转化的细胞。
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