Methods for identification and uses of anti-inflammatory receptors for eicosapentaenoic acid analogs
    53.
    发明授权
    Methods for identification and uses of anti-inflammatory receptors for eicosapentaenoic acid analogs 有权
    用于二十碳五烯酸类似物的抗炎症受体的鉴定和使用方法

    公开(公告)号:US07341840B2

    公开(公告)日:2008-03-11

    申请号:US11218281

    申请日:2005-09-01

    Abstract: The present invention is directed to methods for the identification and uses of receptors that interact with anti-inflammatory compounds derived from eicosapentaenoic acid (EPA). The receptors are of the G-protein coupled receptor (GPCR) family, and are useful to screen candidate substances for anti-inflammatory activity, especially substances that are analogs of EPA. Such analogs are termed “resolvins”; and are typically di- and tri-hydroxy EPA analogs. One analog herein denoted Resolvin E1 was identified in humans and prepared by total synthesis. In nanomolar range Resolvin E1 reduces dermal inflammation, peritonitis, dendritic cells (DCs) migration and IL-12 production. Also described herein is a receptor denoted Reso ER1 that interacts with Resolvin E1 to attenuate cytokine induced activation of inflammatory pathways mediated by transcription factor (NF)-kB. Treatment of DCs with small-interfering RNA specific for ResoE1 eliminated the ligand's ability to regulate IL-12. Assays of anti-inflammatory activity based on these discoveries are also described.

    Abstract translation: 本发明涉及鉴定和使用与二十碳五烯酸(EPA)衍生的抗炎化合物相互作用的受体的方法。 受体是G蛋白偶联受体(GPCR)家族,可用于筛选候选物质的抗炎活性,特别是类似于EPA的物质。 这样的类似物被称为“溶解素”; 并且通常是二羟基和三羟基EPA类似物。 在人类中鉴定了一种在本文中称为Resolvin E1的类似物,并通过全合成制备。 在纳摩尔范围内,Resolvin E1可减少皮肤炎症,腹膜炎,树突细胞(DCs)迁移和IL-12的产生。 本文还描述了称为Reso ER1的受体,其与Resolvin E1相互作用以减弱由转录因子(NF)-kB介导的炎症途径的细胞因子诱导的活化。 用特异于ResoE1的小干扰RNA处理DC消除了配体调节IL-12的能力。 还描述了基于这些发现的抗炎活性测定。

    Cell culture model and applications thereof
    54.
    发明申请
    Cell culture model and applications thereof 有权
    细胞培养模型及其应用

    公开(公告)号:US20070264682A1

    公开(公告)日:2007-11-15

    申请号:US11647436

    申请日:2006-12-29

    Applicant: Isabelle Besne

    Inventor: Isabelle Besne

    CPC classification number: G01N33/5032 G01N33/5058

    Abstract: The present invention relates to a multicellular model comprising at least, as cell type: keratinocytes, melanocytes, and nerve cells, in which the keratinocytes and the melanocytes form a first cell layer, said nerve cells form a second cell layer devoid of physical contact with the first cell layer, said first and second cell layers being arranged so as to be compatible with a manifestation of at least one cellular chemical exchange.

    Abstract translation: 本发明涉及至少包含细胞类型:角质形成细胞,黑素细胞和神经细胞的多细胞模型,其中角质形成细胞和黑素细胞形成第一细胞层,所述神经细胞形成与第二细胞层没有物理接触的第二细胞层 第一细胞层,所述第一和第二细胞层被布置成与至少一种细胞化学交换的表现相容。

    Use of the endo-180 gene and polypeptide for diagnosis and treatment
    55.
    发明申请
    Use of the endo-180 gene and polypeptide for diagnosis and treatment 审中-公开
    使用endo-180基因和多肽进行诊断和治疗

    公开(公告)号:US20070072244A1

    公开(公告)日:2007-03-29

    申请号:US10557089

    申请日:2005-11-16

    CPC classification number: G01N33/5032 G01N33/6872 G01N2333/4724 G01N2333/78

    Abstract: This application is directed to a process of identifying a compound capable of modulating activity of a human ENDO180 receptor that comprises the steps of measuring the binding of the ENDO180 receptor to an interactor with which the ENDO180 receptor interacts specifically in vivo, in the absence or presence of a compound, and determining whether the binding of the ENDO180 receptor to the interactor is affected by the compound. This application is also directed to use of a compound identified by that process in the preparation of a medicament for therapy of disease, in particular fibrosis. This application also relates to the use of ENDO180 modulators in treatment of disease.

    Abstract translation: 本申请涉及鉴定能够调节人ENDO180受体活性的化合物的方法,该方法包括以下步骤:在不存在或存在下测量ENDO180受体与ENDO180受体在体内特异性相互作用的相互作用因子的结合 的化合物,并确定ENDO180受体与相互作用体的结合是否受化合物的影响。 本申请还涉及通过该方法鉴定的化合物在制备用于治疗疾病,特别是纤维化的药物中的用途。 本申请还涉及使用ENDO180调节剂治疗疾病。

    Activated forms of notch and methods based thereon
    56.
    发明申请
    Activated forms of notch and methods based thereon 有权
    基于此的活化形式的缺口和方法

    公开(公告)号:US20070003983A1

    公开(公告)日:2007-01-04

    申请号:US10781059

    申请日:2004-02-17

    CPC classification number: G01N33/5032 C07K14/705 G01N33/68 G01N2500/10

    Abstract: The present invention is directed to methods for detecting or measuring Notch activation by observing or measuring the appearance of Notch on the cell surface or by observing or measuring Notch cleavage products that are indicative of Notch activation. The present invention is also directed to methods for detecting a molecule that modulates Notch activation by observing or measuring a change in the amount of Notch expressed on the cell surface or a change in the amount or pattern of Notch cleavage products. The present invention is also directed to a substantially purified activated heterodimeric form of Notch and components thereof and pharmaceutical compositions and kits thereof. The present invention is based, at least in part, on the discovery that Notch in its active form, i.e., the form that mediates signal transduction and that binds Notch ligands such as Delta, is a heterodimer of an about 180 kDa subunit (NEC) and an about 110 kDa subunit (NTM), which are tethered together through a reducing agent-sensitive linkage, in particular, a non-covalent, metal ion-dependent linkage.

    Abstract translation: 本发明涉及通过观察或测量Notch在细胞表面上的外观或通过观察或测量Notch切割产物来表征Notch活化来检测或测量Notch活化的方法。 本发明还涉及通过观察或测量在细胞表面表达的Notch量的变化或Notch切割产物的量或图案的变化来检测调节Notch活化的分子的方法。 本发明还涉及基本上纯化的Notch及其组分的活化异二聚体形式及其药物组合物和试剂盒。 本发明至少部分地基于以下发现:Notch以其活性形式即介导信号转导并且结合Notch配体如Delta的形式是约180kDa亚基的异二聚体(N < SUP> EC)和约110kDa的亚基(N?TM),它们通过还原剂敏感性连接键连在一起,特别是非共价金属离子依赖性 连锁。

    Screening methods for compounds useful in the treatment of polycystic kidney disease
    58.
    发明授权
    Screening methods for compounds useful in the treatment of polycystic kidney disease 失效
    可用于治疗多囊肾病的化合物的筛选方法

    公开(公告)号:US06638726B1

    公开(公告)日:2003-10-28

    申请号:US09689461

    申请日:2000-10-12

    Abstract: The present invention provides cell-based screening assays designed to identify agents that regulate the activity of the polycystic kidney disease proteins encoded by the PKD-1 and PKD-2 genes and that may be useful in the treatment of polycystic kidney disease. The assays of the invention comprise the contacting of genetically engineered cells expressing a mutant or truncated PKD gene product with a test agent and assaying for a decrease in the PKD mediated mutant phenotype. Characteristics associated with such a mutant phenotype include increased adherence to type I collagen coated surfaces; apical expression of NaK-ATPase on the cell membrane; increased expression of &bgr;-2-NaK-ATPase; and decreased focal adhesion kinase (FAK) incorporation into focal adhesion complexes, and inability to form tubular structures in a gel matrix. To facilitate the screening methods of the invention, cells may be genetically engineered to express epitope tagged PKD gene products and/or epitope tagged PKD interacting proteins (PKD-IP). Such interacting proteins include, for example, focal adhesion complex proteins such as FAK, paxillin, vinculin, talin and the like.

    Abstract translation: 本发明提供基于细胞的筛选试验,其设计用于鉴定调节由PKD-1和PKD-2基因编码的多囊肾疾病蛋白质的活性并可用于治疗多囊肾病的药剂。 本发明的测定包括将表达突变或截短的PKD基因产物的遗传工程改造的细胞与测试试剂接触并测定PKD介导的突变体表型的降低。 与这种突变表型相关的特征包括增加对I型胶原涂层表面的粘附性; NaK-ATP酶在细胞膜上的顶端表达; 增加β-2-NaK-ATP酶的表达; 并且减少粘着斑激酶(FAK)掺入聚焦粘附复合物中,并且不能在凝胶基质中形成管状结构。 为了促进本发明的筛选方法,细胞可以被遗传工程化以表达表位标记的PKD基因产物和/或表位标记的PKD相互作用蛋白(PKD-IP)。 这种相互作用的蛋白质包括例如FAK,桩蛋白,纽蛋白,talin等粘着斑复合蛋白。

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