公开(公告)号：WO2001084160A3

公开(公告)日：2001-11-08

申请号：PCT/US2001/014066

申请日：2001-05-01

Applicant: MITOKOR ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA ,  GIBSON, Bradford, W. ,  GHOSH, Soumitra, S. ,  DAVIS, Robert, E.

Inventor： GIBSON, Bradford, W. ,  GHOSH, Soumitra, S. ,  DAVIS, Robert, E.

IPC: H01J49/04

Abstract: Compositions and methods are provided for identifying oxidative modifications of proteins by mass spectrometric analysis, including MALDI-TOF MS, of protein and peptide fractions of biological samples to determine specific occurrences of nitrotyrosine at amino acid sequence and proteomic levels. Diagnostic methods for diseases characterized by elevated free radicals and oxidative stress, and screening assays for therapeutic agents useful in treating such diseases, are also disclosed.

公开(公告)号：WO0116373A2

公开(公告)日：2001-03-08

申请号：PCT/US0023638

申请日：2000-08-28

Applicant: MITOKOR ,  MURPHY ANNE N ,  WILEY SANDRA EILEEN ,  ANDREYEV ALEXANDER Y

Inventor： MURPHY ANNE N ,  WILEY SANDRA EILEEN ,  ANDREYEV ALEXANDER Y

IPC: G01N33/50 ,  C12Q1/68

CPC classification number: G01N33/5079 ,  G01N33/5008 ,  G01N33/5035 ,  G01N33/5058 ,  G01N33/5076 ,  G01N2510/00

Abstract: Compositions and methods are provided for identifying agents that alter mitochondrial intermembrane space protein (MISP) translocation. The screening methods generally detect agents that alter the level of detectable extramitochondrial MISP following exposure of a cell to an agent known or suspected to induce mitochondrial intermembrane space protein translocation. Such agents may be used, for example, in the treatment of a variety of conditions associated with altered mitochondrial function.

Abstract translation: 提供组合物和方法用于鉴定改变线粒体膜间隙蛋白（MISP）易位的药剂。 筛选方法通常检测在将细胞暴露于已知或怀疑诱导线粒体间膜间质蛋白易位的药剂后改变可检测的线粒体MISP水平的试剂。 这样的试剂可以用于例如治疗与改变的线粒体功能相关的各种病症。

公开(公告)号：WO2004058683A2

公开(公告)日：2004-07-15

申请号：PCT/US2003/041213

申请日：2003-12-19

Applicant: MITOKOR, INC. ,  GHOSH, Soumitra, S. ,  PEI, Yazhong ,  TANG, Xiao-Qing

Inventor： GHOSH, Soumitra, S. ,  PEI, Yazhong ,  TANG, Xiao-Qing

IPC: C07C229/00

CPC classification number: C07C335/16 ,  C07C229/38 ,  C07C233/81 ,  C07C251/24 ,  C07C275/42 ,  C07C311/08

Abstract: Compounds which have utility in the treatment of conditions associated with altered mitochondrial function. The compounds having structure (I), including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein X, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined herein. Pharmaceutical compositions containing a compound of structure (I), as well as methods relating to the use thereof, are also disclosed.

Abstract translation: 可用于治疗与改变的线粒体功能相关的病症的化合物。 具有结构（I）的化合物，包括立体异构体，前药和药学上可接受的盐，其中X，R 1，R 2，R 3，R 4，R 5和R 6如本文所定义。 还公开了含有结构（I）化合物的药物组合物以及与其用途有关的方法。

公开(公告)号：WO2004041286A1

公开(公告)日：2004-05-21

申请号：PCT/US2003/034340

申请日：2003-10-27

Applicant: MITOKOR, INC. ,  YU, Jinghua ,  GHOSH, Soumitra, S. ,  PEI, Yazhong

Inventor： YU, Jinghua ,  GHOSH, Soumitra, S. ,  PEI, Yazhong

IPC: A61K31/5513

CPC classification number: A61K31/5513 ,  C07D243/24

Abstract: The invention provides compositions and methods for altering insulin secretion using a compound that inhibits calcium efflux via the mitochondrial calcium/ sodium antiporter (MCA). Methods of treatment are thereby provided, and are particularly useful for treatment of subjects having, or suspected of being at risk for having, diabetes mellitus.

Abstract translation: 本发明提供使用通过线粒体钙/钠反转运体（MCA）抑制钙流出的化合物来改变胰岛素分泌的组合物和方法。 从而提供了治疗方法，并且特别可用于治疗患有或怀疑患有糖尿病风险的受试者。

公开(公告)号：WO02068680A3

公开(公告)日：2003-10-16

申请号：PCT/US0206090

申请日：2002-02-27

Applicant: MITOKOR ,  ANDERSON CHRISTEN M ,  CLEVENGER WILLIAM

Inventor： ANDERSON CHRISTEN M ,  CLEVENGER WILLIAM

IPC: A61K38/00 ,  C07K14/47 ,  C12N15/62 ,  C12Q1/34 ,  G01N33/50 ,  G01N33/573 ,  G01N33/74 ,  C12N15/87

CPC classification number: G01N33/5091 ,  A61K38/00 ,  C07K14/4703 ,  C07K2319/00 ,  C07K2319/04 ,  C07K2319/07 ,  C07K2319/10 ,  C07K2319/21 ,  C12N15/62 ,  C12Q1/34 ,  G01N33/5008 ,  G01N33/5014 ,  G01N33/502 ,  G01N33/5044 ,  G01N33/5067 ,  G01N33/507 ,  G01N33/5076 ,  G01N33/5079 ,  G01N33/573 ,  G01N33/74 ,  G01N2333/914 ,  G01N2500/00

Abstract: The present invention provides compositions and methods for altering mitochondrial ATP metabolism, including compositions having fusion proteins comprising IF1 polypeptide-derived sequences, as well as binding and functional assays exploiting IF1 interactions with ATP synthase. Also disclosed are methods for identifying an agent capable of reducing mitochondrial ATP hydrolysis and/or increasing mitochondrial ATP synthesis, including pharmaceutical compositions identified by such methods. The invention also provides methods for treating diabetes, and in particular, type 2 DM, using an agent identified according to the disclosed methods.

Abstract translation: 本发明提供了用于改变线粒体ATP代谢的组合物和方法，包括具有包含IF1多肽衍生序列的融合蛋白的组合物，以及利用与ATP合酶的IF1相互作用的结合和功能测定。 还公开了用于鉴定能够减少线粒体ATP水解和/或增加线粒体ATP合成的试剂的方法，包括通过这些方法鉴定的药物组合物。 本发明还提供了使用根据所公开的方法鉴定的药剂治疗糖尿病，特别是2型DM的方法。

公开(公告)号：WO0240996A9

公开(公告)日：2003-10-02

申请号：PCT/US0146699

申请日：2001-11-08

Applicant: MITOKOR ,  HWANG JUNG-JOO ,  BECKER DAVID K ,  DAVIS ROBERT E

Inventor： HWANG JUNG-JOO ,  BECKER DAVID K ,  DAVIS ROBERT E

IPC: G01N33/50 ,  G01N33/68 ,  C12Q1/68 ,  A61K48/00

CPC classification number: G01N33/6896 ,  C07K16/18 ,  C07K2317/34 ,  G01N33/5011 ,  G01N33/5014

Abstract: The present invention provides methods and compositions for screening assays for compounds that alter mitochondrial function, and in particular that alter apoptosis, based on the observations that expression of the transcription factor FREAC-2 is up-regulated in Alzheimer's disease and that induction of FREAC-2 expression in a cell results in apoptosis. The invention thus provides methods for identifying agents that alter mitochondrial function by determining the activity of reducing or enhancing apoptosis that follows the induced expression of FREAC-2, useful, for example, in treatment of neurodegenerative diseases (e.g., Alzheimer's) and/or of diseases of inappropriate cell proliferation or survival (e.g., cancer). The present invention also includes methods of identifying pharmaceutical/ molecular targets for compounds that alter mitochondrial function (e.g., by altering apoptosis).

Abstract translation: 本发明提供了用于筛选针对改变线粒体功能的化合物的测定方法和组合物，特别是基于在阿尔茨海默氏病中上调转录因子FREAC-2的表达和FREAC- 2在细胞中的表达导致细胞凋亡。 因此，本发明提供了通过确定减少或增强FREAC-2诱导表达后的凋亡的活性来鉴定改变线粒体功能的药物的方法，例如可用于治疗神经变性疾病（例如阿尔茨海默病）和/或 不适当的细胞增殖或存活的疾病（如癌症）。 本发明还包括鉴定改变线粒体功能（例如通过改变细胞凋亡）的化合物的药物/分子靶标的方法。

公开(公告)号：WO0240996A3

公开(公告)日：2003-07-10

申请号：PCT/US0146699

申请日：2001-11-08

Applicant: MITOKOR ,  HWANG JUNG-JOO ,  BECKER DAVID K ,  DAVIS ROBERT E

Inventor： HWANG JUNG-JOO ,  BECKER DAVID K ,  DAVIS ROBERT E

IPC: G01N33/50 ,  G01N33/68 ,  C12Q1/68 ,  A61K48/00

CPC classification number: G01N33/6896 ,  C07K16/18 ,  C07K2317/34 ,  G01N33/5011 ,  G01N33/5014

Abstract: The present invention provides methods and compositions for screening assays for compounds that alter mitochondrial function, and in particular that alter apoptosis, based on the observations that expression of the transcription factor FREAC-2 is up-regulated in Alzheimer's disease and that induction of FREAC-2 expression in a cell results in apoptosis. The invention thus provides methods for identifying agents that alter mitochondrial function by determining the activity of reducing or enhancing apoptosis that follows the induced expression of FREAC-2, useful, for example, in treatment of neurodegenerative diseases (e.g., Alzheimer's) and/or of diseases of inappropriate cell proliferation or survival (e.g., cancer). The present invention also includes methods of identifying pharmaceutical/ molecular targets for compounds that alter mitochondrial function (e.g., by altering apoptosis).

Abstract translation: 本发明提供了用于筛选测定化合物的方法和组合物，所述化合物改变线粒体功能，特别是改变细胞凋亡，基于观察到转录因子FREAC-2的表达在阿尔茨海默病中上调，并且诱导FREAC- 2在细胞中的表达导致细胞凋亡。 因此，本发明提供了通过确定在诱导表达FREAC-2之后降低或增强细胞凋亡的活性来鉴定改变线粒体功能的试剂的方法，其可用于例如治疗神经退行性疾病（例如阿尔茨海默病）和/或 不适当的细胞增殖或存活的疾病（例如癌症）。 本发明还包括鉴定改变线粒体功能（例如通过改变细胞凋亡）的化合物的药物/分子靶的方法。

公开(公告)号：WO02068381A3

公开(公告)日：2002-10-31

申请号：PCT/US0206717

申请日：2002-02-27

Applicant: MITOKOR ,  GHOSH SOUMITRA S ,  SZABO TOMAS R

Inventor： GHOSH SOUMITRA S ,  SZABO TOMAS R

IPC: C07D295/12 ,  A61K31/155 ,  A61K31/277 ,  A61K31/5375 ,  A61P3/10 ,  A61P17/06 ,  A61P19/02 ,  A61P21/00 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  A61P27/02 ,  A61P27/16 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07C279/28

CPC classification number: A61K31/5375 ,  A61K31/155 ,  C07C279/28

Abstract: Compounds, compositions and methods treating arthritic disorders such as osteoarthritis or rheumatoid arthritis, and for treating other diseases associated with altered mitochondrial function, such as cancer, psoriasis, stroke, Alzheimer's Disease and diabetes.

Abstract translation: 治疗关节炎疾病如骨关节炎或类风湿性关节炎的化合物，组合物和方法，以及用于治疗与线粒体功能改变相关的其它疾病，例如癌症，牛皮癣，中风，阿尔茨海默氏病和糖尿病。

公开(公告)号：WO0055323A9

公开(公告)日：2001-11-15

申请号：PCT/US0007311

申请日：2000-03-16

Applicant: MITOKOR ,  HERRNSTADT CORRINA ,  MILLER SCOTT W ,  DAVIS ROBERT E

Inventor： HERRNSTADT CORRINA ,  MILLER SCOTT W ,  DAVIS ROBERT E

IPC: G01N33/50 ,  A61K31/7088 ,  A61K38/00 ,  A61K45/00 ,  A61K48/00 ,  A61P25/28 ,  C07K14/47 ,  C12N15/09 ,  C12N15/10 ,  C12N15/12 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/15 ,  C12N5/10 ,  G01N33/53

CPC classification number: C12N15/1072 ,  C07K14/47 ,  C07K14/4711

Abstract: Compositions and methods are provided for identifying factors, including organellar factors, that are differentially expressed when cells in different states, such as metabolic, respiratory, disease or apoptotic states, are compared. In preferred embodiments the invention relates to mitochondria DNA depleted ( rho ) and cytoplasmic hybrid (cybrid) cells, such as mitochondrial cybrid cells. Use of the invention to identify species specific expression of organellar factors such as organelle associated macromolecules is contemplated. Also disclosed are examples of organellar factors that are differentially expressed in organelle associated disease, including a variety of human genes that are differentially expressed in Alzheimer's disease.

Abstract translation: 提供了组合物和方法，用于鉴别比较不同状态的细胞如代谢，呼吸，疾病或凋亡状态时差异表达的因子，包括细胞因子。 在优选的实施方案中，本发明涉及线粒体DNA耗尽（rhoO）和细胞质杂交（cybrid）杂交细胞，如线粒体细胞杂交细胞。 预期本发明用于鉴定细胞器因子如细胞器相关大分子的物种特异性表达的用途。 还公开了在细胞器相关疾病中差异表达的细胞因子的实例，包括在阿尔茨海默氏病中差异表达的各种人基因。

公开(公告)号：WO0120536A2

公开(公告)日：2001-03-22

申请号：PCT/US0025304

申请日：2000-09-15

Applicant: MITOKOR ,  FAHY EOIN DAVID

Inventor： FAHY EOIN DAVID

IPC: G06F19/20 ,  G06F19/24 ,  G06F19/00

CPC classification number: G06F19/24 ,  G06F19/20

Abstract: A system and corresponding method analyzes biological data for sets of test subjects such as gene arrays of group test subjects into clusters and order the clusters into a hierarchy based on similarities and differences of biological data corresponding to the test subjects. A combination of nonhierarchical clustering and hierarchical clustering methods is used to efficiently and effectively perform hierarchical clustering of such biological data as highly dense gene arrays containing many thousand test subjects such as genes. First the test subjects are nonhierarchically clustered according to similarities and differences of their biological data as determined by distance techniques. Representative values, such as mean values, of the biological data are determined for each nonhierarchical cluster of test subjects. These representative values are then used to hierarchically cluster the nonhierarchical clusters. Biological data for each test subject is displayed in a row of a table. The rows of the table are arranged by the nonhierarchical clustering and further by the hierarchical clustering. Each value of the biological data is color coded according to its value to display patterns in the hierarchically clustered biological data.

Abstract translation: 系统和相应的方法将组测试受试者的测试对象的集合的生物数据分析为群集，并且基于与测试对象相对应的生物数据的相似性和差异将簇排序成层次结构。 使用非分层聚类和层次聚类方法的组合来有效地和有效地执行这样的生物数据的分层聚类，如包含数千个测试对象如基因的高密度基因阵列。 首先，根据通过距离技术确定的生物数据的相似性和差异，测试对象是非层次聚类的。 针对每个测试对象的非分层聚类确定生物数据的代表性值，如平均值。 然后将这些代表性值用于对非分层集群进行分层聚类。 每个测试对象的生物数据显示在一行表中。 表的行由非分层聚类排列，进一步由层次聚类排列。 生物数据的每个值根据其价值进行颜色编码，以显示分层聚类生物数据中的模式。