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1. 发明授权

US07488587B2 Histone deacetylase and methods of use thereof 有权
标题翻译：组蛋白脱乙酰酶及其使用方法
公开(公告)号：US07488587B2
公开(公告)日：2009-02-10
申请号：US10175559
申请日：2002-06-17
申请人： Eric Verdin , Wolfgang Fischle , Franck O. Dequiedt
发明人： Eric Verdin , Wolfgang Fischle , Franck O. Dequiedt
IPC分类号： C07H21/00 , C07H21/02
CPC分类号： C12N9/16 , A61K38/00 , C07K2319/00
摘要： The present invention provides nucleic acid molecules that encode histone deacetylase, as well as recombinant vectors and host cells that include the subject nucleic acid molecules. Also provided are histone deacetylase polypeptide compositions. The histone deacteylase nucleic acid molecules are useful in a variety of diagnostic and therapeutic applications, which are also provided.
摘要翻译：本发明提供了编码组蛋白脱乙酰酶的核酸分子，以及包含受试核酸分子的重组载体和宿主细胞。还提供了组蛋白脱乙酰酶多肽组合物。组蛋白去活化酶核酸分子可用于各种诊断和治疗应用，其也被提供。

2. 发明申请

US20090061015A1 Regulation of Protein Activity By Reversible Acetylation 失效
标题翻译：通过可逆乙酰化调节蛋白质活性
公开(公告)号：US20090061015A1
公开(公告)日：2009-03-05
申请号：US11761198
申请日：2007-06-11
申请人： Bjoern Schwer , Eric Verdin
发明人： Bjoern Schwer , Eric Verdin
IPC分类号： A61K33/00 , G01N33/53 , C12N5/02
CPC分类号： G01N33/502 , G01N33/573
摘要： This invention discloses the first cellular acetylated substrate protein of SIRT3, Acetyl-CoA synthetase 2 (AceCS2), which is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at lysine 642 (Lys642) in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. Thus, a mammalian sirtuin directly controls the activity of a metabolic enzyme via reversible lysine acetylation. Modulators of the acetylation status or the activity of AceCS2 are useful for the treatment of pathological conditions, such as type II diabetes, hypercholesterolemia, hyperlipidemia, and obesity.
摘要翻译：本发明公开了作为线粒体基质蛋白质的SIRT3的第一细胞乙酰化底物蛋白，乙酰辅酶A合成酶2（AceCS2）。 AceCS2在酶的活性位点的赖氨酸642（Lys642）处可逆地乙酰化。线粒体sirtuin SIRT3在体外和体内都与AceCS2和脱乙酰基Lys642相互作用。通过SIRT3对AceCS2的脱乙酰化激活了AceCS2的乙酰辅酶A合成酶活性。因此，哺乳动物沉默调节蛋白通过可逆赖氨酸乙酰化直接控制代谢酶的活性。乙酰化状态或AceCS2活性的调节剂可用于治疗病理状况，如II型糖尿病，高胆固醇血症，高脂血症和肥胖症。

3. 发明申请

US20050287597A1 Compositions and methods for modulating sirtuin activity 有权
标题翻译：调节sirtuin活性的组合物和方法
公开(公告)号：US20050287597A1
公开(公告)日：2005-12-29
申请号：US11022192
申请日：2004-12-22
申请人： Melanie Ott , Eric Verdin , Manfred Jung
发明人： Melanie Ott , Eric Verdin , Manfred Jung
IPC分类号： C12Q1/26 , C12Q1/34 , C12Q1/70 , G01N33/53
CPC分类号： C12Q1/34 , C12Q1/26 , G01N2333/16 , G01N2333/918 , G01N2333/98 , G01N2500/02
摘要： The present invention provides treatment methods involving modulating a sirtuin activity and/or a sirtuin mRNA and/or a sirtuin polypeptide level. In some embodiments, the present invention provides treatment methods involving modulating SIRT1 activity and/or SIRT mRNA and/or polypeptide level. The present invention provides methods of inhibiting SIRT1 Tat deacetylase activity. Methods of inhibiting SIRT1 Tat deacetylase activity are useful for treating immunodeficiency virus infections, particularly human immunodeficiency virus (HIV) infection. Thus, the present invention provides methods of treating an immunodeficiency virus infection, generally involving inhibiting SIRT1 Tat deacetylase activity. The present invention further provides methods of identifying agents that modulate sirtuin activity (e.g., SIRT1 activity), particularly ability of sirtuins to interact with (e.g., bind and/or deacetylate) a substrate, e.g., a viral substrate such as a Tat polypeptide. The present invention further provides active agents that modulate sirtuin activity or expression; and compositions, including pharmaceutical compositions, comprising the active agents.
摘要翻译：本发明提供了涉及调节沉默调节蛋白的活性和/或sirtuin mRNA和/或sirtuin多肽水平的治疗方法。在一些实施方案中，本发明提供了涉及调节SIRT1活性和/或SIRT mRNA和/或多肽水平的治疗方法。本发明提供抑制SIRT1 Tat脱乙酰酶活性的方法。抑制SIRT1 Tat脱乙酰酶活性的方法可用于治疗免疫缺陷病毒感染，特别是人类免疫缺陷病毒（HIV）感染。因此，本发明提供了治疗免疫缺陷病毒感染的方法，通常涉及抑制SIRT1 Tat脱乙酰酶的活性。本发明进一步提供了鉴定调节沉默调节蛋白的活性（例如，SIRT1活性）的药剂的方法，特别是sirtuins与底物（例如，结合和/或脱乙酰化）例如病毒底物如Tat多肽的能力。本发明还提供调节沉默调节蛋白的活性或表达的活性剂; 和包含活性剂的组合物，包括药物组合物。

4. 发明授权

US07589167B2 ZA loops of bromodomains 有权
标题翻译：溴结构域的ZA环
公开(公告)号：US07589167B2
公开(公告)日：2009-09-15
申请号：US09784553
申请日：2001-02-16
申请人： Ming-Ming Zhou , Aneel K. Aggarwal , Eric Verdin , Melanie Ott
发明人： Ming-Ming Zhou , Aneel K. Aggarwal , Eric Verdin , Melanie Ott
IPC分类号： C07K2/00 , C07K7/00 , C07K14/00
CPC分类号： A61K31/198 , C07K2299/00 , C12N9/1029 , C12Y203/01048 , G01N33/56988 , G01N2333/163 , G01N2500/02
摘要： The present invention provides the structural determination of a bromodomain determined by NMR spectroscopy. The present invention also provides binding partners for the bromodomain. The present invention further provides the structural determination of the Tat-P/CAF binding complex determined by NMR spectroscopy. In addition, the present invention provides methodology for related drug discovery using high throughput drug screening or structure based rational drug design using the three-dimensional data.
摘要翻译：本发明提供了通过NMR光谱测定的溴结构域的结构测定。本发明还提供了溴结构域的结合配偶体。本发明还提供了通过NMR光谱测定的Tat-P / CAF结合复合物的结构测定。此外，本发明提供使用高通量药物筛选或使用三维数据的基于结构的合理药物设计的相关药物发现的方法。

5. 发明申请

US20060051815A1 Methods of treating smooth muscle cell disorders 审中-公开
标题翻译：平滑肌细胞疾病的治疗方法
公开(公告)号：US20060051815A1
公开(公告)日：2006-03-09
申请号：US11166669
申请日：2005-06-23
申请人： Eric Verdin , David Waltregny , Vincent Castronovo
发明人： Eric Verdin , David Waltregny , Vincent Castronovo
IPC分类号： C12Q1/68 , G01N33/567 , G01N33/53
CPC分类号： G01N33/5061 , C12Q1/6881 , C12Q2600/112 , C12Q2600/136 , C12Q2600/158 , G01N33/57434 , G01N33/57442 , G01N33/57446 , G01N33/57492 , G01N33/6887
摘要： The present invention provides methods of detecting cells showing smooth muscle differentiation. The present invention further provides methods of detecting tumor cells. The present invention further provides compositions and methods for treating smooth muscle cell disorders.
摘要翻译：本发明提供检测显示平滑肌分化的细胞的方法。本发明还提供了检测肿瘤细胞的方法。本发明还提供了治疗平滑肌细胞病症的组合物和方法。

6. 发明授权

US07482016B2 Immunogenic compositions comprising HIV-1 acetylated Tat polypeptides 有权
标题翻译：包含HIV-1乙酰化Tat多肽的免疫原性组合物
公开(公告)号：US07482016B2
公开(公告)日：2009-01-27
申请号：US10799854
申请日：2004-03-12
申请人： Alexander P. Doerr , Melanie Ott , Eric Verdin
发明人： Alexander P. Doerr , Melanie Ott , Eric Verdin
IPC分类号： A61K39/21 , A61K39/385
CPC分类号： C07K14/005 , A61K39/00 , A61K39/12 , A61K39/21 , A61K2039/545 , A61K2039/55516 , A61K2039/55566 , C07K16/1072 , C12N2740/16322 , C12N2740/16334
摘要： The present invention provides compositions, including immunogenic compositions, comprising acetylated Tat protein of an immunodeficiency virus. The present invention further provides antibodies that specifically bind an acetylated Tat polypeptide. The present invention further provides methods of inducing an immune response to an immunodeficiency virus Tat protein in an individual. The present invention further provides methods of inhibiting transcriptional activation of an immunodeficiency virus in a cell of an individual.
摘要翻译：本发明提供了包含免疫原性组合物的组合物，其包含免疫缺陷病毒的乙酰化的Tat蛋白。本发明还提供了特异性结合乙酰化Tat多肽的抗体。本发明还提供了诱导针对个体的免疫缺陷病毒Tat蛋白的免疫应答的方法。本发明还提供了抑制个体细胞中免疫缺陷病毒转录激活的方法。

7. 发明申请

US20080076835A1 METHODS OF MODULATING MITOCHONDRIAL NAD-DEPENDENT DEACETYLASE 审中-公开
公开(公告)号：US20080076835A1
公开(公告)日：2008-03-27
申请号：US11839292
申请日：2007-08-15
申请人： Eric Verdin , Brian North , Bjoern Schwer
发明人： Eric Verdin , Brian North , Bjoern Schwer
IPC分类号： G01N33/53 , A61K45/06 , C12Q1/68
CPC分类号： C12Q1/48 , C12Q1/34 , G01N2500/00
摘要： The present invention provides methods for identifying agents that modulate a level or an activity of a mitochondrial NAD-dependent deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating mitochondrial NAD-dependent deacetylase activity in a cell. The invention further provides methods of modulating mitochondrial function by modulating the activity of mitochondrial NAD-dependent deacetylase.

8. 发明授权

US08518635B2 Regulation of protein activity by reversible acetylation 失效
标题翻译：通过可逆乙酰化调节蛋白质活性
公开(公告)号：US08518635B2
公开(公告)日：2013-08-27
申请号：US11761198
申请日：2007-06-11
申请人： Bjoern Schwer , Eric Verdin
发明人： Bjoern Schwer , Eric Verdin
IPC分类号： C12Q1/00
CPC分类号： G01N33/502 , G01N33/573
摘要： This invention discloses the first cellular acetylated substrate protein of SIRT3, Acetyl-CoA synthetase 2 (AceCS2), which is a mitochondrial matrix protein. AceCS2 is reversibly acetylated at lysine 642 (Lys642) in the active site of the enzyme. The mitochondrial sirtuin SIRT3 interacts with AceCS2 and deacetylates Lys642 both in vitro and in vivo. Deacetylation of AceCS2 by SIRT3 activates the acetyl-CoA synthetase activity of AceCS2. Thus, a mammalian sirtuin directly controls the activity of a metabolic enzyme via reversible lysine acetylation. Modulators of the acetylation status or the activity of AceCS2 are useful for the treatment of pathological conditions, such as type II diabetes, hypercholesterolemia, hyperlipidemia, and obesity.
摘要翻译：本发明公开了作为线粒体基质蛋白质的SIRT3的第一细胞乙酰化底物蛋白，乙酰辅酶A合成酶2（AceCS2）。 AceCS2在酶的活性位点的赖氨酸642（Lys642）处可逆地乙酰化。线粒体sirtuin SIRT3在体外和体内都与AceCS2和脱乙酰基Lys642相互作用。通过SIRT3对AceCS2的脱乙酰化激活了AceCS2的乙酰辅酶A合成酶活性。因此，哺乳动物沉默调节蛋白通过可逆赖氨酸乙酰化直接控制代谢酶的活性。乙酰化状态或AceCS2活性的调节剂可用于治疗病理状况，如II型糖尿病，高胆固醇血症，高脂血症和肥胖症。

9. 发明申请

US20120028912A1 Methods of modulating bromodomains 审中-公开
标题翻译：调节溴结构域的方法
公开(公告)号：US20120028912A1
公开(公告)日：2012-02-02
申请号：US12590069
申请日：2009-11-02
申请人： Ming-Ming Zhou , Aneel K. Aggarwal , Melanie Ott , Eric Verdin
发明人： Ming-Ming Zhou , Aneel K. Aggarwal , Melanie Ott , Eric Verdin
IPC分类号： A61K38/10 , A61K31/135 , A61P31/18 , A61K31/16 , A61K31/352 , A61K38/08 , A61K31/195
CPC分类号： A61K9/0078 , A61K31/00 , A61K38/08 , A61K38/10 , A61K38/21 , A61K2300/00
摘要： The present invention features compounds useful for and methods for preventing or inhibiting the binding of bromodomains to acetyl-lysine residues of proteins and methods for treating HIV infection and HIV related disease.
摘要翻译：本发明的特征在于可用于预防或抑制溴结构域与蛋白质的乙酰赖氨酸残基的结合的方法和用于治疗HIV感染和HIV相关疾病的方法。

10. 发明申请

US20080200566A1 Dephosphorylation of HDAC7 By Myosin Phosphatase 审中-公开
标题翻译：通过肌球蛋白磷酸酶对HDAC7的脱磷酸化
公开(公告)号：US20080200566A1
公开(公告)日：2008-08-21
申请号：US11741561
申请日：2007-04-27
申请人： Eric Verdin , Maribel Parra
发明人： Eric Verdin , Maribel Parra
IPC分类号： A61K35/00 , C12Q1/42 , A61P11/06 , A61P9/00 , C12Q1/68
CPC分类号： C12Q1/42 , C12Q1/44 , G01N33/5023 , G01N33/573 , G01N2500/02 , G01N2500/04 , G01N2510/00 , G01N2800/122 , G01N2800/32
摘要： The present invention relates to screening methods that make use of a histone deacetylase interacting with a myosin phosphatase for the identification of novel therapeutics useful for inhibiting or inducing apoptosis and for the treatment of pathological conditions, such as smooth muscle cell disorder, cardiac hypertrophy or asthma. Also disclosed are methods for inhibiting or inducing apoptosis and for treatment of a pathological condition by administering to a mammal a therapeutically effective amount of a compound that inhibits or increases the dephosphorylation of a histone deacetylase by a myosin phosphatase or inhibits or increases the binding of a histone deacetylase to a myosin phosphatase.
摘要翻译：本发明涉及利用与肌球蛋白磷酸酶相互作用的组蛋白脱乙酰酶鉴定可用于抑制或诱导细胞凋亡和治疗病理状况如平滑肌细胞病症，心脏肥大或哮喘的新治疗剂的筛选方法。还公开了通过向哺乳动物施用治疗有效量的通过肌球蛋白磷酸酶抑制或增加组蛋白脱乙酰酶的去磷酸化的化合物或抑制或增加结合的方法来抑制或诱导凋亡和治疗病理状况的方法组蛋白脱乙酰酶对肌球蛋白磷酸酶。

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