Therapeutic combinations of RAR antagonists and RXR agonists and use thereof
    1.
    发明授权
    Therapeutic combinations of RAR antagonists and RXR agonists and use thereof 有权
    RAR拮抗剂和RXR激动剂的治疗组合及其应用

    公开(公告)号:US06653322B1

    公开(公告)日:2003-11-25

    申请号:US09619308

    申请日:2000-07-19

    IPC分类号: A61K3147

    CPC分类号: A61K45/06

    摘要: The present invention provides compositions and methods for treating an animal, preferably a human, suffering from or predisposed to a physical disorder by administering an effective amount of a composition comprising at least one RAR antagonist, preferably an RAR&agr; antagonist, and at least one RXR agonist. The combination of an RXR agonist, which has no therapeutic effects alone, with an RAR antagonist allows the use of lower doses of the RAR antagonist than were previously thought to be efficacious; this approach obviates many of the undesirable physiological side-effects of treatment with RAR antagonists.

    摘要翻译: 本发明提供了通过施用有效量的包含至少一种RAR拮抗剂,优选RARalpha拮抗剂的组合物和至少一种RXR激动剂来治疗患有或易患身体障碍的动物,优选人的组合物和方法 。 没有治疗作用的RXR激动剂与RAR拮抗剂的组合允许使用比先前认为有效的更低剂量的RAR拮抗剂; 这种方法避免了用RAR拮抗剂治疗的许多不期望的生理副作用。

    Polynucleotide encoding transcriptional intermediary factor-2
    3.
    发明授权
    Polynucleotide encoding transcriptional intermediary factor-2 失效
    多核苷酸编码转录中介因子-2

    公开(公告)号:US06268173B1

    公开(公告)日:2001-07-31

    申请号:US08891640

    申请日:1997-07-11

    IPC分类号: C12N1511

    CPC分类号: C07K14/4702

    摘要: The present invention concerns a nuclear receptor (NR) transcriptional mediator. More specifically, isolated nucleic acid molecules are provided encoding transcriptional intermediary factor-2 (TIF2). Recombinant methods for making TIF2 polypeptides are also provided as are TIF2 antibodies. Screening methods are also provided for identifying agonists and antagonists of the activation function AF-2 of nuclear receptors, for identifying agonists and antagonists of the AD1 activation domain activity of TIF2, and for identifying agonists and antagonists of the AD2 activation domain activity of TIF2.

    摘要翻译: 本发明涉及核受体(NR)转录介体。 更具体地,提供编码转录中介因子-2(TIF2)的分离的核酸分子。 还提供了用于制备TIF2多肽的重组方法,如TIF2抗体。 还提供筛选方法用于鉴定核受体的激活功能AF-2的激动剂和拮抗剂,用于鉴定TIF2的AD1活化域活性的激动剂和拮抗剂,以及用于鉴定TIF2的AD2活化域活性的激动剂和拮抗剂。

    Transcriptional intermediary factor-2
    4.
    发明授权
    Transcriptional intermediary factor-2 有权
    转录中介因子-2

    公开(公告)号:US06861508B2

    公开(公告)日:2005-03-01

    申请号:US09842256

    申请日:2001-04-26

    IPC分类号: C07K14/47 C12N15/12 C07K14/00

    CPC分类号: C07K14/4702

    摘要: The present invention concerns a nuclear receptor (NR) transcriptional mediator. More specifically, isolated nucleic acid molecules are provided encoding transcriptional intermediary factor-2 (TIF2). Recombinant methods for making TIF2 polypeptides are also provided as are TIF2 antibodies. Screening methods are also provided for identifying agonists and antagonists of the activation function AF-2 of nuclear receptors, for identifying agonists and antagonists of the AD1 activation domain activity of TIF2, and for identifying agonists and antagonists of the AD2 activation domain activity of TIF2.

    摘要翻译: 本发明涉及核受体(NR)转录介体。 更具体地,提供编码转录中介因子-2(TIF2)的分离的核酸分子。 还提供了用于制备TIF2多肽的重组方法,如TIF2抗体。 还提供筛选方法用于鉴定核受体的激活功能AF-2的激动剂和拮抗剂,用于鉴定TIF2的AD1活化域活性的激动剂和拮抗剂,以及用于鉴定TIF2的AD2活化域活性的激动剂和拮抗剂。

    Process for Identifying Novel Anti-Inflammatory Molecules with Reduced Direct Transrepression of Genes Induced by Glucocorticoids
    5.
    发明申请
    Process for Identifying Novel Anti-Inflammatory Molecules with Reduced Direct Transrepression of Genes Induced by Glucocorticoids 审中-公开
    识别具有减少由糖皮质激素诱导的基因直接转录的新型抗炎分子的方法

    公开(公告)号:US20140093884A1

    公开(公告)日:2014-04-03

    申请号:US14111495

    申请日:2012-04-13

    IPC分类号: G01N33/50

    CPC分类号: G01N33/5023 C12Q1/6897

    摘要: The present invention relates to a new process for identifying novel anti-inflammatory molecules with reduced direct transrepression of genes induced by glucocorticoids.The inventors have discovered that GCs-mediated transrepression can be mediated not only via the tethering indirect pathway, but also through direct binding of GR to “simple” negative GREs (nGRE), which belongs to a novel family of evolutionary-conserved cis-acting negative response elements (IR nGREs), and are found in numerous GC-repressed genes.

    摘要翻译: 本发明涉及用糖皮质激素诱导的基因直接逆转抑制来鉴定新的抗炎分子的新方法。 本发明人已经发现,GCs介导的转录抑制不仅可以通过连接间接途径介导,而且可以通过将GR直接结合到“简单的”负的GRE(nGRE),其属于进化保守的顺式作用的新家族 负反应元件(IR nGRE),并且在许多GC抑制基因中发现。

    Steroid/thyroid hormone receptor-related gene, which is inappropriately
expressed in human heptocellular carcinoma, and which is a retinoic
acid receptor
    7.
    发明授权
    Steroid/thyroid hormone receptor-related gene, which is inappropriately expressed in human heptocellular carcinoma, and which is a retinoic acid receptor 失效
    类固醇/甲状腺激素受体相关基因,其在人肝细胞癌中不适当地表达,并且其是视黄酸受体

    公开(公告)号:US5376530A

    公开(公告)日:1994-12-27

    申请号:US95706

    申请日:1993-07-22

    IPC分类号: C07K14/705 C12Q1/68

    摘要: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta.. The RAR-.beta. gene is transcriptionally up-regulated by retinoic acid (RA) and its promoter region may contain a RARE (retinoic acid responsive element).

    摘要翻译: 将以前分离的乙型肝炎病毒(HBV)整合到与肝细胞癌(HCC)连接的147bp细胞DNA片段中作为探针从人肝cDNA文库克隆相应的互补DNA。 核苷酸序列分析显示,已命名为hap的细胞基因的整体结构与DNA结合激素受体的结构相似。 7例肝癌和肝癌细胞系中有6例表达2.5 kb的hap mRNA,在正常成人和胎儿肝脏中检测不到,但存在于所有非肝脏组织中。 低严格杂交实验揭示了人类基因组中hap相关基因的存在。 克隆的DNA序列可用于制备纯hap蛋白,并用作检测和分离互补DNA和RNA序列的探针。 hap蛋白是鉴定为RAR-β的视黄酸(RA)受体。 RAR-β基因由视黄酸(RA)转录上调,其启动子区域可能含有RARE(视黄酸反应元件)。

    METHOD FOR TEMPORALLY CONTROLLING THE BIOLOGICAL ACTIVITY OF PROTEINS IN VERTEBRATES, AND APPLICATIONS THEREOF
    10.
    发明申请
    METHOD FOR TEMPORALLY CONTROLLING THE BIOLOGICAL ACTIVITY OF PROTEINS IN VERTEBRATES, AND APPLICATIONS THEREOF 有权
    温度控制蛋白质生物活性的方法及其应用

    公开(公告)号:US20120052570A1

    公开(公告)日:2012-03-01

    申请号:US13145752

    申请日:2010-01-22

    IPC分类号: C12N5/071

    摘要: The present invention relates to a method for tightly temporally controlling the biological activity of a protein of interest in a vertebrate, upon induction of the activity of a fusion protein comprising said protein of interest and an ERM polypeptide containing a mutated ligand binding domain of the human oestrogen receptor α, with a synthetic ligand that does not interfere with oestrogen signalling. In particular, the present invention concerns a method for generating tightly temporally-controlled targeted somatic mutations in a vertebrate, preferably a mouse, by inducing the activity of a fusion protein comprising a site-specific recombinase protein and an ERM polypeptide, with a synthetic ligand devoid of oestrogenic and anti-oestrogenic activities.

    摘要翻译: 本发明涉及在诱导包含所述目的蛋白质的融合蛋白的活性和含有人的突变配体结合结构域的ERM多肽时紧密地暂时地控制脊椎动物中感兴趣的蛋白质的生物学活性的方法 雌激素受体α与不影响雌激素信号传导的合成配体。 特别地,本发明涉及通过用合成配体诱导包含位点特异性重组酶蛋白和ERM多肽的融合蛋白的活性,在脊椎动物,优选小鼠中产生紧密的时间控制的靶向体细胞突变的方法 没有雌激素和抗雌激素活性。