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    MOLECULAR FLUX RATES THROUGH CRITICAL PATHWAYS MEASURED BY STABLE ISOTOPE LABELING IN VIVO, AS BIOMARKERS OF DRUG ACTION AND DISEASE ACTIVITY
    3.
    发明申请
    MOLECULAR FLUX RATES THROUGH CRITICAL PATHWAYS MEASURED BY STABLE ISOTOPE LABELING IN VIVO, AS BIOMARKERS OF DRUG ACTION AND DISEASE ACTIVITY 有权
    通过作为药物作用和疾病活动的生物标记的生物体内稳定同位素标记测量的关键路径的分子量

    公开(公告)号：US20120115127A1

    公开(公告)日：2012-05-10

    申请号：US13215110

    申请日：2011-08-22

    申请人： Marc K. HELLERSTEIN

    发明人： Marc K. HELLERSTEIN

    IPC分类号： C12Q1/68 ,  C07H21/04

    CPC分类号： G01N33/6881 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5014 ,  G01N33/5038 ,  G01N33/5088 ,  G01N33/58 ,  G01N33/60 ,  G01N33/6887 ,  G01N33/6893 ,  G01N33/92 ,  G01N2500/00 ,  G01N2800/042 ,  G01N2800/044 ,  G01N2800/323

    摘要： The methods described herein enable the evaluation of compounds on subjects to assess their therapeutic efficacy or toxic effects. The target of analysis is the underlying biochemical process or processes (i.e., metabolic process) thought to be involved in disease pathogenesis. Molecular flux rates within the one or more biochemical processes serve as biomarkers and are quantitated and compared with the molecular flux rates (i.e., biomarker) from control subjects (i.e., subjects not exposed to the compounds). Any change in the biomarker in the subject relative to the biomarker in the control subject provides information to evaluate therapeutic efficacy of an administered drug or a toxic effect and to develop the compound further if desired. In one aspect of the invention, stable isotope-labeled substrate molecules are administered to a subject and the label is incorporated into targeted molecules in a manner that reveals molecular flux rates through metabolic pathways of interest.

    摘要翻译： 本文描述的方法能够评估受试者的化合物以评估其治疗功效或毒性作用。 分析的目标是被认为参与疾病发病机制的潜在的生化过程或过程（即代谢过程）。 一个或多个生物化学过程中的分子通量率用作生物标志物，并且与来自对照受试者（即未暴露于化合物的受试者）的分子通量速率（即，生物标志物）进行定量比较。 相对于对照受试者中的生物标志物，对象中生物标志物的任何变化提供了评估给药的药物或毒性作用的治疗功效的信息，并且如果需要，进一步开发化合物。 在本发明的一个方面，将稳定的同位素标记的底物分子施用于受试者，并且以通过感兴趣的代谢途径揭示分子通量速率的方式将标记并入靶向分子中。

    METHOD FOR HIGH-THROUGHPUT SCREENING OF COMPOUNDS AND COMBINATIONS OF COMPOUNDS FOR DISCOVERY AND QUANTIFICATION OF ACTIONS, PARTICULARLY UNANTICIPATED THERAPEUTIC OR TOXIC ACTIONS, IN BIOLOGICAL SYSTEMS
    4.
    发明申请
    METHOD FOR HIGH-THROUGHPUT SCREENING OF COMPOUNDS AND COMBINATIONS OF COMPOUNDS FOR DISCOVERY AND QUANTIFICATION OF ACTIONS, PARTICULARLY UNANTICIPATED THERAPEUTIC OR TOXIC ACTIONS, IN BIOLOGICAL SYSTEMS 有权
    用于化合物的高通量筛选和化合物的组合的方法用于发现和定量的生物系统中的特别是非化学治疗或毒性作用的行为

    公开(公告)号：US20110195865A1

    公开(公告)日：2011-08-11

    申请号：US13031084

    申请日：2011-02-18

    申请人： Marc K. HELLERSTEIN

    发明人： Marc K. HELLERSTEIN

    IPC分类号： C40B30/06

    CPC分类号： G01N33/5067 ,  A61K49/0008 ,  G01N33/5088 ,  G01N33/60 ,  G01N33/6848 ,  Y02A90/22

    摘要： The invention enables high-throughput screening of compounds in living systems to detect unanticipated or unintended biological actions. The invention also allows for screening, detection, and confirmation of new indications for approved drugs. Screening and detection of toxic effects of compounds also can be achieved by using the methods of the invention. The methods comprise administering isotope-labeled substrates to a living system so that the label is incorporated into molecules in a manner that reveals flux rates through metabolic pathways thought to be involved in a disease. Comparisons between living systems exposed to compounds and living systems not so exposed reveals the effects of the compounds on the flux rates through the metabolic pathways. Combinations or mixtures of compounds can be systematically screened to detect unanticipated or unintended biological actions, including synergistic actions, in the same manner.

    摘要翻译： 本发明使得生物系统中化合物的高通量筛选能够发现未预期的或非预期的生物作用。 本发明还允许筛选，检测和确认经批准的药物的新适应症。 化合物的毒性作用的筛选和检测也可以通过使用本发明的方法来实现。 所述方法包括向活体系统施用同位素标记的底物，使得将标记以通过被认为参与疾病的代谢途径揭示通量速率的方式并入分子中。 暴露于化合物的活体系与未暴露的生物体系之间的比较揭示了化合物对通过代谢途径的通量速率的影响。 可以以相同的方式系统地筛选化合物的组合或混合物以检测意外的或非预期的生物作用，包括协同作用。

    METHODS FOR DETERMINING THE METABOLISM OF SUGARS AND FATS IN AN INDIVIDUAL
    5.
    发明申请
    METHODS FOR DETERMINING THE METABOLISM OF SUGARS AND FATS IN AN INDIVIDUAL 有权
    用于确定个体中糖和脂肪代谢的方法

    公开(公告)号：US20100041082A1

    公开(公告)日：2010-02-18

    申请号：US12403331

    申请日：2009-03-12

    申请人： Marc K. HELLERSTEIN

    发明人： Marc K. HELLERSTEIN

    IPC分类号： G01N33/50 ,  C12Q1/54

    CPC分类号： G01N33/58 ,  A61K49/0004

    摘要： Provided herein are methods for determining the metabolism of one or more sugars and/or fatty acids, and applications thereof. Such applications include determining the rate of glycogen synthesis and glycolysis, which are believed to be early markers for predicting elevated risk of diabetes and cardiovascular disease. Other applications include methods for screening drugs that effect sugar and/or fatty acid metabolism. The methods are useful for at least partially characterizing drugs for desirable or undesirable (toxic) characteristics. Drugs that are at least partially characterized using the methods of the invention can then be further developed in pre-clinical testing and clinical trials. Such drugs may be found to be useful in treating obesity, diabetes, cardiovascular disease, and other disorders of metabolism.

    摘要翻译： 本文提供了确定一种或多种糖和/或脂肪酸的代谢的方法及其应用。 这些应用包括确定糖原合成和糖酵解的速率，这被认为是预测糖尿病和心血管疾病风险升高的早期标志物。 其他应用包括用于筛选影响糖和/或脂肪酸代谢的药物的方法。 所述方法可用于至少部分表征药物以获得期望的或不期望的（有毒的）特征。 可以在临床前临床试验和临床试验中进一步开发使用本发明方法至少部分表征的药物。 可以发现这些药物可用于治疗肥胖，糖尿病，心血管疾病和其他代谢紊乱。