公开(公告)号：JP2005130867A

公开(公告)日：2005-05-26

申请号：JP2005039891

申请日：2005-02-16

Applicant: Mitokor ,  マイトコー

Inventor： MURPHY ANNE N ,  STOUT AMY K

IPC: C12Q1/02

Abstract: PROBLEM TO BE SOLVED: To obtain an improved composition and to provide an improved method for modulating mitochondria calcium homeostasis in consideration of the importance of mitochondria modulation with intracellular calcium and the relationship of mitochondria activity with disease conditions, and to provide an assay for specifically detecting medicines for changing mitochondria calcium modulation so as to provide improved treatment of these diseases. SOLUTION: The method for identifying medicines for changing mitochondria functions comprises following steps; (a) a step for contacting, in each of reaction vessels in a high throughput screening array, (i) a biological sample containing cells comprising cytosol, mitochondria and calcium indicator molecules with (ii) a source of calcium cation under a condition capable of keeping mitochondria membrane potential, wherein the calcium indicator molecules can generate detectable signal proportional to calcium level in the cytosol, (b) a step for detecting, in each reacting vessel and at plural time points, signals generated by the calcium indicator molecules, (c) a step for comparing signals generated by the calcium indicator molecules in the absence of the candidate medicine at one or more time points with signals generated by the calcium indicator molecules in the presence of the candidate medicine at one or more time points and, thereby, identifying the medicine for changing mitochondria functions. COPYRIGHT: (C)2005,JPO&NCIPI

Abstract translation: 要解决的问题：考虑到线粒体调节与细胞内钙的重要性以及线粒体活性与疾病状况的关系，获得改进的组合物并提供调节线粒体钙稳态的改进方法，并提供测定 用于特异性检测用于改变线粒体钙调节的药物，以便改善这些疾病的治疗。 解决方案：用于鉴定改变线粒体功能的药物的方法包括以下步骤： （a）在高通量筛选阵列的每个反应容器中接触每个反应容器的步骤，（i）包含细胞质，线粒体和钙指示剂分子的细胞的生物样品与（ii）能够在 保持线粒体膜电位，其中钙指示剂分子可以产生与细胞质中钙水平成比例的可检测信号，（b）在每个反应容器中和在多个时间点检测由钙指示剂分子产生的信号的步骤，（c ）在一个或多个时间点，在候选药物的存在下，在一个或多个时间点将与由钙指示剂分子产生的信号的钙指示剂分子产生的信号进行比较， 鉴定改变线粒体功能的药物。 版权所有（C）2005，JPO＆NCIPI

公开(公告)号：JP2004154139A

公开(公告)日：2004-06-03

申请号：JP2003408115

申请日：2003-12-05

Applicant: Mitokor ,  マイトコー

Inventor： ANDERSON CHRISTEN M ,  DAVIS ROBERT E ,  CLEVENGER WILLIAM ,  WILEY SANDRA EILEEN ,  MILLER SCOTT W ,  SZABO TOMAS R ,  GHOSH SOUMITRA S

IPC: G01N33/50 ,  A61K31/704 ,  A61K31/7048 ,  A61K31/7056 ,  A61K31/7064 ,  A61K45/00 ,  A61P3/00 ,  A61P3/10 ,  A61P17/06 ,  A61P25/08 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  A61P27/16 ,  A61P35/00 ,  A61P43/00 ,  C07H15/256 ,  C07H15/26 ,  C07K1/22 ,  C07K14/47 ,  C07K19/00 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12N15/62 ,  C12P21/02 ,  C12Q1/02 ,  C12Q1/68 ,  G01N33/15 ,  G01N33/53 ,  G01N33/566

CPC classification number: C07K14/47 ,  C07K2319/00 ,  C07K2319/07 ,  C07K2319/21 ,  C07K2319/23 ,  C12N15/62 ,  C12N2799/021

Abstract: PROBLEM TO BE SOLVED: To produce an adenine nucleotide translocator (ANT) having reliability for being used in various purposes in an enough amount for the same, to provide a composition capable of producing an ANT protein including an ANT fusion protein, to provide a method for producing the composition, to provide a new ANT ligand, to provide a method for identifying and isolating the ANT protein, and to identify and isolate an agent interacting with the ANT. SOLUTION: A recombinant expression construct contains at least one promoter which is combined with a nucleic acid molecule containing a first nucleic acid sequence and a second nucleic acid sequence so as to be actuated, wherein the first nucleic acid sequence encodes an ANT polypeptide of an animal. Further, the ANT polypeptide is expressed in the expression construct as the fusion protein with a polypeptide product of the second nucleic acid sequence. COPYRIGHT: (C)2004,JPO

公开(公告)号：US20040067987A1

公开(公告)日：2004-04-08

申请号：US10386154

申请日：2003-03-11

Applicant: MitoKor

Inventor： Soumitra S. Ghosh ,  Tomas R. Szabo

IPC: A61K031/44 ,  A61K031/40 ,  A61K031/16 ,  C07D213/57 ,  C07D207/46

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. The compounds of this invention have the following structure (I): 1 including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein R1-5 are as defined herein. The methods of this invention are directed to administering to a warm-blooded animal in need thereof an effective amount of a compound of structure (I), typically in the form of a pharmaceutical composition.

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。 本发明的化合物具有以下结构（I）：包括其立体异构体，前药和药学上可接受的盐，其中R1-5如本文所定义。 本发明的方法涉及向有需要的温血动物施用有效量的结构式（I）的化合物，通常为药物组合物的形式。

公开(公告)号：US20020173543A1

公开(公告)日：2002-11-21

申请号：US10020090

申请日：2001-12-14

Applicant: MitoKor

Inventor： Yazhong Pei ,  Walter H. Moos ,  Soumitra S. Ghosh

IPC: A61K031/24 ,  A61K031/195 ,  C07C229/40

CPC classification number: C07C235/20 ,  C07C237/22 ,  C07C237/42 ,  C07D307/68

Abstract: Compounds for treating diseases by altering mitochondrial function that affects cellular processes, as well as to compositions and methods related thereto. The compounds have the structure 1 wherein R1, R2, R3 and A are as defined herein.

Abstract translation: 通过改变影响细胞过程的线粒体功能来治疗疾病的化合物，以及与其相关的组合物和方法。 化合物具有其中R 1，R 2，R 3和A如本文所定义的结构。

公开(公告)号：US20040241801A1

公开(公告)日：2004-12-02

申请号：US10763398

申请日：2004-01-23

Applicant: MitoKor, Inc.

Inventor： Christen M. Anderson ,  Amy Karen Carroll

IPC: C12N009/22 ,  C07H021/04 ,  C12N015/85

CPC classification number: C07K14/47 ,  C07H15/24 ,  C07J31/006 ,  C07K16/18 ,  C07K2319/00 ,  C07K2319/07 ,  C07K2319/21 ,  C07K2319/23 ,  C12N15/62 ,  C12N2799/021 ,  C12N2799/026

Abstract: Compositions and methods are provided for producing adenine nucleotide translocator (ANT) polypeptides and fusion proteins, including the production and use of recombinant expression constructs having a regulated promoter. ANT ligands and compositions and methods for identifying ANT ligands, agents that bind ANT and agents that interact with ANT are also disclosed.

Abstract translation: 提供了用于产生腺嘌呤核苷酸转运蛋白（ANT）多肽和融合蛋白的组合物和方法，包括产生和使用具有调节启动子的重组表达构建体。 还公开了ANT配体以及用于鉴定ANT配体的组合物和方法，结合ANT的试剂和与ANT相互作用的试剂。

公开(公告)号：US20040029122A1

公开(公告)日：2004-02-12

申请号：US10218191

申请日：2002-08-12

Applicant: MitoKor, Inc.

Inventor： Corinna Herrnstadt ,  Eoin D. Fahy

IPC: C12Q001/68 ,  G06F019/00 ,  G01N033/48 ,  G01N033/50

CPC classification number: G16B20/00 ,  G16B30/00 ,  G16B50/00

Abstract: A computer implemented glucose utilization defect (GUD) risk assessment system and method screens individuals for GUD risk based upon their mitochondrial DNA sequence. A data input receives sample data, which is compared by a deviation determiner against the standard mitochondrial DNA reference to generate a binary output sequence containing difference positions indicating deviations between the sample data and the standard reference. A deviation analyzer then assesses GUD risk by analyzing the binary sequence output with respect to ranges of mitochondrial DNA positions as identified by pre-screen ranges stored in a pre-screen ranges database and GUD ranges stored in a GUD ranges database. The GUD ranges found in the GUD database are further determined by a reference string analysis method or a branch point analysis method performed by the GUD risk assessment system and method.

Abstract translation: 计算机实施葡萄糖利用缺陷（GUD）风险评估系统和方法根据其线粒体DNA序列筛选个体的GUD风险。 数据输入接收样本数据，其通过偏差确定器与标准线粒体DNA参考进行比较，以生成包含指示样本数据和标准参考之间的偏差的差异位置的二进制输出序列。 偏差分析仪然后通过分析存储在存储在GUD范围数据库中的预筛选范围数据库和GUD范围内的预筛选范围所确定的线粒体DNA位置的范围，分析二进制序列输出来评估GUD风险。 GUD数据库中的GUD范围进一步由GUD风险评估系统和方法执行的参考字符串分析方法或分支点分析方法进行确定。

公开(公告)号：US20030176448A1

公开(公告)日：2003-09-18

申请号：US10233051

申请日：2002-08-30

Applicant: MitoKor

Inventor： Soumitra S. Ghosh ,  Scott W. Miller ,  Robert E. Davis ,  Walter H. Moos

IPC: A61K031/505 ,  A61K031/4178 ,  A61K031/4172 ,  A61K031/416 ,  A61K031/415 ,  A61K031/35 ,  A61K031/353 ,  A61K031/192 ,  A61K031/155

CPC classification number: A61K31/155 ,  A61K31/00 ,  A61K31/05 ,  A61K31/06 ,  A61K31/136 ,  C07C39/08 ,  C07C39/11 ,  C07C39/19 ,  C07C69/017 ,  C07C215/78 ,  C07C215/80 ,  C07C217/84 ,  C07C279/18 ,  C07D215/20 ,  C07D311/72

Abstract: The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases that may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus, Parkinson's Disease, neuronal and cardiac ischemia, Huntington's disease and stroke.

Abstract translation: 本发明一般涉及用于治疗线粒体功能障碍导致组织变性的线粒体保护剂，更具体地涉及与其相关的化合物，组合物和方法。 本发明的方法涉及向有需要的温血动物施用药学有效量的线粒体保护剂，本发明的组合物含有与药学上可接受的载体或稀释剂组合的线粒体保护剂。 可以通过本发明治疗的线粒体相关疾病包括（但不限于）阿尔茨海默氏病，糖尿病，帕金森病，神经元和心脏缺血，亨廷顿病和中风。

公开(公告)号：US20040192740A1

公开(公告)日：2004-09-30

申请号：US10741595

申请日：2003-12-19

Applicant: MitoKor, Inc. ,  Pfizer Inc.

Inventor： Soumitra S. Ghosh ,  Yazhong Pei ,  Xiao-Qing Tang ,  Spiros Liras ,  Michael K. Ahlijanian

IPC: C07D213/57 ,  A61K031/44 ,  A61K031/277 ,  C07C255/40

CPC classification number: C07D263/57 ,  A61K31/185 ,  C07C65/24 ,  C07C65/30 ,  C07C65/40 ,  C07C69/94 ,  C07D277/66 ,  C07D307/80 ,  C07D333/16 ,  C07D333/24 ,  C07D333/56 ,  C07D333/60

Abstract: Compounds which have utility in the treatment of conditions associated with altered mitochondrial function. The compounds have the following structure (I): 1 including stereoisomers, prodrugs, and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5 and R6 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。 所述化合物具有以下结构（I）：包括立体异构体，前药和其药学上可接受的盐，其中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：US20040146892A1

公开(公告)日：2004-07-29

申请号：US10684232

申请日：2003-10-10

Applicant: MitoKor, Inc.

Inventor： Anne N. Murphy ,  William Clevenger ,  Sandra Eileen Wiley ,  Alexander Y. Andreyev ,  Luciano G. Frigeri ,  Gonul Velicelebi ,  Robert E. Davis

IPC: C12Q001/68 ,  C07H021/04

CPC classification number: G01N33/5079 ,  C07K14/43595 ,  C07K2319/00 ,  C07K2319/21 ,  C07K2319/23 ,  C07K2319/50 ,  C07K2319/60 ,  C12N9/90 ,  C12N15/62 ,  G01N33/542

Abstract: Compositions and methods are provided for identifying agents that alter mitochondrial membrane permeability transition. The screening methods generally detect agents that alter the interaction between the mitochondrial adenine nucleotide translocator and cyclophilin D. 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通透性转换的药剂。 筛选方法通常检测改变线粒体腺嘌呤核苷酸转运体和亲环蛋白D之间的相互作用的试剂。这种试剂可用于例如治疗与线粒体功能改变相关的多种病症。

公开(公告)号：US20020082193A1

公开(公告)日：2002-06-27

申请号：US09960612

申请日：2001-09-20

Applicant: MitoKor

Inventor： Christen M. Anderson ,  Robert E. Davis ,  Yazhong Pei ,  Soumitra S. Ghosh

IPC: A61K031/00

CPC classification number: A61K45/06 ,  A61K31/554 ,  A61K2300/00

Abstract: The invention provides compositions and methods for altering insulin secretion using an agent 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. Compositions and methods related to the identification of gene sequences encoding the mitochondrial calcium/sodium antiporter, expression of such sequences and screening assays using expressed MCA products are also provided.

Abstract translation: 本发明提供使用通过线粒体钙/钠反转录酶（MCA）抑制钙流出的药剂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。 还提供了与识别编码线粒体钙/钠反转录酶的基因序列，这种序列的表达以及使用表达的MCA产物的筛选测定相关的组合物和方法。