公开(公告)号：US20050084840A1

公开(公告)日：2005-04-21

申请号：US10502279

申请日：2003-01-22

申请人： Hideki Endoh ,  Ryosuke Nakano ,  Eiji Kurosaki ,  Miyuki Kato ,  Hiroyuki Yokota ,  Kazunori Inabe

发明人： Hideki Endoh ,  Ryosuke Nakano ,  Eiji Kurosaki ,  Miyuki Kato ,  Hiroyuki Yokota ,  Kazunori Inabe

IPC分类号： A61P3/10 ,  C12N1/19 ,  C12N1/21 ,  C12N15/10 ,  C12N15/12 ,  C12Q1/68 ,  G01N33/566 ,  C12N1/18 ,  C12N15/74 ,  C12Q1/00

CPC分类号： G01N33/566 ,  C12N15/1055 ,  C12Q1/6897 ,  G01N2333/70567

摘要： Disclosing a method for screening a protein interactive with PPAR in a ligand-dependent manner, works as a useful tool for screening a drug ameliorating insulin resistance. By the method, ECHLP as a main action ligand-dependent PPAR binding molecule, FLJ13111 as a main action ligand-selective factor interactive with PPARγ and AOP2 as an adverse action ligand-dependent PPAR binding molecule were obtained. By using ECHLP interactive with PPAR, FLJ13111 interactive with PPAR and AOP2 interactive with PPAR, a screening system for a drug ameliorating insulin resistance is constructed and disclosed, the drug giving selectively the main action with no occurrence of the adverse action. Additionally, a method for producing a pharmaceutical composition for ameliorating insulin resistance is disclosed, which contains as the active component, a promoting agent of the main action through PPAR, an agonist specific to the main action through PPAR, an inhibitor of ECHLP interactive with PPAR to promote the main action through PPAR, a substance suppressing the adverse action through PPARγ, an inhibitor of AOP2 interactive with PPAR to suppress the adverse action through PPARγ, an activating agent of FLJ13111 interactive with PPAR to promote the main action through PPAR or an activator of FLJ13111 expression.

摘要翻译： 披露以配体依赖的方式筛选与PPAR相互作用的蛋白质的方法，其作为筛选改善胰岛素抵抗的药物的有用工具。 通过该方法，获得了作为主要作用配体依赖性PPAR结合分子的ECHLP，FLJ13111作为与PPARgamma和AOP2作为不利作用配体依赖性PPAR结合分子相互作用的主要作用配体选择性因子。 通过使用ECHLP与PPAR交互，FLJ13111与PPAR和AOP2交互式与PPAR交互，构建并公开了改善胰岛素抵抗的药物筛选系统，该药物选择性地给予主要作用，不发生不良反应。 另外，公开了一种制备用于改善胰岛素抵抗的药物组合物的方法，其包含通过PPAR作为主要作用的主要作用的促进剂，通过PPAR主要作用的激动剂，与PPAR相互作用的ECHLP抑制剂 通过PPAR促进PPAR的主要作用，PPARgamma是与PPAR相互作用的AOP2抑制剂，通过PPARgamma的抑制剂来抑制不良反应，PPARgamma是与PPAR相互作用的FLJ13111激活剂，通过PPAR或激活剂促进主要作用 的FLJ13111表达。

公开(公告)号：US20060211041A1

公开(公告)日：2006-09-21

申请号：US10537767

申请日：2003-12-04

申请人： Yuki Endo ,  Hideki Endoh ,  Yoshitaka Ueda ,  Miyuki Kato ,  Kazunori Inabe

发明人： Yuki Endo ,  Hideki Endoh ,  Yoshitaka Ueda ,  Miyuki Kato ,  Kazunori Inabe

IPC分类号： G01N33/53 ,  C07H21/04 ,  C07K14/705

CPC分类号： G01N33/5041 ,  C07K14/47 ,  G01N33/5008 ,  G01N33/573 ,  G01N2500/00

摘要： A novel polypeptide useful in screening an insulin resistance improving agent and a carbohydrate metabolism improving agent, a polynucleotide coding for the aforementioned polypeptide, an expression vector comprising the aforementioned polynucleotide, and a cell transfected with the aforementioned expression vector are disclosed. The aforementioned polypeptide is a protein which is expressed in fat, and the activity of Akt2 is reduced in a fat cell in which the protein is highly expressed. A method for screening an insulin resistance improving agent and a carbohydrate metabolism improving agent using the aforementioned polypeptide, and a method for producing a pharmaceutical composition for insulin resistance improvement and carbohydrate metabolism improvement, which uses a substance obtained by said screening method as the active ingredient, are disclosed.

摘要翻译： 公开了一种可用于筛选胰岛素抵抗改善剂和碳水化合物代谢改善剂的新型多肽，编码上述多肽的多核苷酸，包含上述多核苷酸的表达载体和用上述表达载体转染的细胞。 上述多肽是在脂肪中表达的蛋白质，并且Akt2的活性在蛋白质高度表达的脂肪细胞中降低。 使用上述多肽筛选胰岛素抵抗性提高剂和碳水化合物代谢改善剂的方法，以及使用通过所述筛选方法获得的物质作为活性成分的胰岛素抵抗改善和碳水化合物代谢改善用药物组合物的制造方法 ，被披露。

公开(公告)号：US07452983B2

公开(公告)日：2008-11-18

申请号：US10537767

申请日：2003-12-04

申请人： Yuki Endo ,  Hideki Endoh ,  Yoshitaka Ueda ,  Miyuki Kato ,  Kazunori Inabe

发明人： Yuki Endo ,  Hideki Endoh ,  Yoshitaka Ueda ,  Miyuki Kato ,  Kazunori Inabe

IPC分类号： C07H21/04 ,  C12N15/63 ,  C12N15/85 ,  C12N15/86 ,  C12N1/21 ,  C12N5/14 ,  C12N1/20 ,  C07K14/00

CPC分类号： G01N33/5041 ,  C07K14/47 ,  G01N33/5008 ,  G01N33/573 ,  G01N2500/00

摘要： A novel polypeptide, a polynucleotide, an expression vector, a cell transfected with the expression vector, a method for screening an insulin resistance improving agent and a carbohydrate metabolism improving agent, and a method for producing a pharmaceutical composition are provided. The polypeptide is useful in screening an insulin resistance improving agent and a carbohydrate metabolism improving agent. When the polypeptide is overexpressed in a fat cell, the activity of Akt2 is reduced. Fat cells express the polypeptide. The polynucleotide encodes the polypeptide. The expression vector includes the polynucleotide. The screening method uses the polypeptide to screen for an insulin resistance improving agent and a carbohydrate metabolism improving agent. The production method uses the substance obtained by the screening method as the active ingredient of the pharmaceutical composition. The pharmaceutical composition is useful for insulin resistance improvement and carbohydrate metabolism improvement.

摘要翻译： 提供新型多肽，多核苷酸，表达载体，用表达载体转染的细胞，筛选胰岛素抵抗性改善剂和碳水化合物代谢改善剂的方法，以及制备药物组合物的方法。 该多肽可用于筛选胰岛素抵抗改善剂和碳水化合物代谢改善剂。 当多肽在脂肪细胞中过表达时，Akt2的活性降低。 脂肪细胞表达多肽。 多核苷酸编码多肽。 表达载体包括多核苷酸。 筛选方法使用多肽筛选胰岛素抵抗改善剂和碳水化合物代谢改善剂。 生产方法使用通过筛选方法获得的物质作为药物组合物的活性成分。 该药物组合物可用于胰岛素抵抗改善和碳水化合物代谢改善。

公开(公告)号：US20060008857A1

公开(公告)日：2006-01-12

申请号：US10530886

申请日：2003-10-09

申请人： Tamaki Oda ,  Hideki Endoh ,  Yoshitaka Ueda ,  Kazunori Inabe

发明人： Tamaki Oda ,  Hideki Endoh ,  Yoshitaka Ueda ,  Kazunori Inabe

IPC分类号： G01N33/574 ,  C07K16/30

CPC分类号： C07K14/4705 ,  C07K14/47

摘要： A novel polypeptide which is useful in screening of an agent for improving insulin resistance and an agent for improving glucose metabolism, a polynucleotide encoding the polypeptide, an expression vector comprising the polynucleotide, and a cell transformed with the expression vector are disclosed. The polypeptide is a protein expressed in skeletal muscle. When the protein is overexpressed, incorporation of sugar into a cell is inhibited. A method for screening of an agent for improving insulin resistance and/or an agent for improving glucose metabolism in which the polypeptide is used, and a method for producing a pharmaceutical composition for insulin resistance and/or glucose metabolism improvement comprising a substance obtained according to the method for screening as an active ingredient are also disclosed.

公开(公告)号：US07141650B2

公开(公告)日：2006-11-28

申请号：US10530886

申请日：2003-10-09

申请人： Tamaki Oda ,  Hideki Endoh ,  Yoshitaka Ueda ,  Kazunori Inabe

发明人： Tamaki Oda ,  Hideki Endoh ,  Yoshitaka Ueda ,  Kazunori Inabe

IPC分类号： A61K14/00

CPC分类号： C07K14/4705 ,  C07K14/47

摘要： A novel polypeptide which is useful in screening of an agent for improving insulin resistance and an agent for improving glucose metabolism, a polynucleotide encoding the polypeptide, an expression vector comprising the polynucleotide, and a cell transformed with the expression vector are disclosed. The polypeptide is a protein expressed in skeletal muscle. When the protein is overexpressed, incorporation of sugar into a cell is inhibited.A method for screening of an agent for improving insulin resistance and/or an agent for improving glucose metabolism in which the polypeptide is used, and a method for producing a pharmaceutical composition for insulin resistance and/or glucose metabolism improvement comprising a substance obtained according to the method for screening as an active ingredient are also disclosed.

摘要翻译： 公开了可用于筛选改善胰岛素抵抗的药剂和改善葡萄糖代谢的药剂的新型多肽，编码多肽的多核苷酸，包含多核苷酸的表达载体和用表达载体转化的细胞。 多肽是在骨骼肌中表达的蛋白质。 当蛋白质过表达时，将糖掺入细胞被抑制。 筛选用于改善胰岛素抵抗的药剂的方法和/或其中使用多肽的改善葡萄糖代谢的药剂，以及制备用于胰岛素抵抗和/或葡萄糖代谢改善的药物组合物的方法，包括根据 还公开了作为活性成分的筛选方法。

公开(公告)号：US08003331B2

公开(公告)日：2011-08-23

申请号：US11909031

申请日：2006-08-09

申请人： Hideki Endoh ,  Hiroyuki Yokota ,  Masahiko Hayakawa ,  Shinji Soga

发明人： Hideki Endoh ,  Hiroyuki Yokota ,  Masahiko Hayakawa ,  Shinji Soga

IPC分类号： G01N33/53

CPC分类号： G01N33/6803 ,  G01N2500/04 ,  G01N2800/042

摘要： A method for identifying a target protein of a compound having a pharmacological action by detecting a tertiary structural change of a target protein by binding a compound having a pharmacological action to a target protein with the use of a molecular chaperone protein having a characteristic of binding to a protein by recognizing a tertiary structural change of the protein is disclosed. Further, a method for screening a therapeutic agent for diabetes using a target protein of biguanide which is a therapeutic agent for diabetes and was found by the identification method, a screening tool which can be used in the screening method and a pharmaceutical composition for treating diabetes containing a substance obtained by the screening method are disclosed.

摘要翻译： 一种用于通过使用具有结合特征的分子伴侣蛋白质将具有药理作用的化合物与靶蛋白结合来检测靶蛋白的三级结构变化来鉴定具有药理作用的化合物的靶蛋白的方法 公开了通过识别蛋白质的三级结构变化的蛋白质。 此外，使用可以用于筛选方法的筛选工具和用于治疗糖尿病的药物组合物，通过鉴别方法，可以使用糖尿病治疗剂的双胍靶蛋白筛选糖尿病治疗剂的方法 公开了通过筛选方法得到的物质。

公开(公告)号：US20090041754A1

公开(公告)日：2009-02-12

申请号：US11909031

申请日：2006-08-09

申请人： Hideki Endoh ,  Hiroyuki Yokota ,  Masahiko Hayakawa ,  Shinji Soga

发明人： Hideki Endoh ,  Hiroyuki Yokota ,  Masahiko Hayakawa ,  Shinji Soga

IPC分类号： A61K39/395 ,  G01N33/68 ,  G01N33/567 ,  C12Q1/48 ,  C07K2/00 ,  C07H21/00 ,  C12N5/06

CPC分类号： G01N33/6803 ,  G01N2500/04 ,  G01N2800/042

摘要： A method for identifying a target protein of a compound having a pharmacological action by detecting a tertiary structural change of a target protein by binding a compound having a pharmacological action to a target protein with the use of a molecular chaperone protein having a characteristic of binding to a protein by recognizing a tertiary structural change of the protein is disclosed. Further, a method for screening a therapeutic agent for diabetes using a target protein of biguanide which is a therapeutic agent for diabetes and was found by the identification method, a screening tool which can be used in the screening method and a pharmaceutical composition for treating diabetes containing a substance obtained by the screening method are disclosed.

摘要翻译： 一种用于通过使用具有结合特征的分子伴侣蛋白质将具有药理作用的化合物与靶蛋白结合来检测靶蛋白的三级结构变化来鉴定具有药理作用的化合物的靶蛋白的方法 公开了通过识别蛋白质的三级结构变化的蛋白质。 此外，使用可以用于筛选方法的筛选工具和用于治疗糖尿病的药物组合物，通过鉴别方法，可以使用糖尿病治疗剂的双胍靶蛋白筛选糖尿病治疗剂的方法 公开了通过筛选方法得到的物质。

公开(公告)号：US20070015155A1

公开(公告)日：2007-01-18

申请号：US10547365

申请日：2004-08-05

申请人： Hideki Endoh ,  Yoshitaka Ueda

发明人： Hideki Endoh ,  Yoshitaka Ueda

IPC分类号： C12Q1/68 ,  G01N33/567 ,  C07H21/04 ,  C12P21/06 ,  C07K14/72

CPC分类号： C07K14/4713 ,  C07K14/47

摘要： The present invention provides a method of screening a drug for improving type 2 diabetes. A protein CbAP40 binding to c-Cbl is found out. It is further found out that mouse CbAP40 gene shows a remarkable increase in expression amount in the muscle of diabetes model mice compared with a normal individual and glucose incorporation is inhibited by overexpressing human CbAP40 gene in a muscle-origin cell, thereby clarifying that the above protein is a factor causative of diabetic conditions. Moreover, the promoter region of human CbAP40 gene is identified and it is clarified that a transcription-inducing activity originating in this promoter region is inhibited by a thiazolidine derivative that improves insulin resistance. Based on these findings, systems for screening a substance having an effect of improving insulin resistance, in which a change of promoter activity and a change in the interaction between c-Cbl and CbAP40 are indicators, are constructed.

摘要翻译： 本发明提供筛选用于改善2型糖尿病的药物的方法。 发现结合c-Cbl的蛋白CbAP40。 进一步发现，与正常个体相比，小鼠CbAP40基因在糖尿病模型小鼠的肌肉中的表达量显着增加，并且通过在肌肉起源的细胞中过表达人CbAP40基因抑制葡萄糖并入，从而澄清上述 蛋白质是导致糖尿病病症的因素。 此外，鉴定人CbAP40基因的启动子区域，并且阐明源自该启动子区域的转录诱导活性被改善胰岛素抵抗的噻唑烷衍生物抑制。 基于这些发现，构建了用于筛选具有改善胰岛素抵抗的作用的物质的系统，其中启动子活性的变化和c-Cbl和CbAP40之间的相互作用的变化是指示剂。

公开(公告)号：US20050244829A1

公开(公告)日：2005-11-03

申请号：US10519447

申请日：2003-07-01

申请人： Makoto Ogino ,  Hideki Endoh

发明人： Makoto Ogino ,  Hideki Endoh

IPC分类号： A61P3/08 ,  C07K14/47 ,  G01N33/50 ,  C12Q1/68 ,  C12N1/18 ,  C12Q1/66

CPC分类号： G01N33/5023 ,  C07K14/4702 ,  C07K2319/71 ,  C07K2319/80 ,  G01N33/5008

摘要： A method for identifying and screening a novel substance promoting the transcription induction activity of PPARγ and improving insulin resistance by promoting the interaction between PPAR promoting the transcription induction activity of PPARγ and p68 RNA helicase and/or promoting the expression of p68RNA helicase is disclosed. The method is a new type method for screening an agent for improving insulin resistance by promoting the transcription induction activity of PPARγ which is different from the conventional PPAR agonist. Furthermore, the method for producing a pharmaceutical composition for improving insulin resistance which comprises the substance obtainable by the above method for screening as an active ingredient is disclosed.

摘要翻译： 公开了通过促进PPARγ和p68 RNA解旋酶的转录诱导活性和/或促进p68RNA解旋酶表达的PPAR之间的相互作用来鉴定和筛选促进PPARγ的转录诱导活性的新物质并提高胰岛素抵抗的方法。 该方法是通过促进与常规PPAR激动剂不同的PPARγ的转录诱导活性来筛选改善胰岛素抵抗的药剂的新型方法。 此外，公开了包含通过上述筛选方法获得的物质作为活性成分的用于改善胰岛素抵抗的药物组合物的制备方法。