Drug for treating states related to the inhibition of angiogenesis and/or endothelial cell proliferation
    1.
    发明申请
    Drug for treating states related to the inhibition of angiogenesis and/or endothelial cell proliferation 失效
    用于治疗与抑制血管发生和/或内皮细胞增殖有关的状态的药物

    公开(公告)号:US20110009310A1

    公开(公告)日:2011-01-13

    申请号:US12660886

    申请日:2010-03-05

    摘要: Soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in chick and mouse and thereby inhibits human tumor growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble non glycosylated CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumors using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues are presented.

    摘要翻译: 可溶性重组CD44透明质酸结合结构域(CD44HABD)抑制小鼠和小鼠的体内血管生成,从而抑制各种起源的人肿瘤生长。 CD44-HABD的抗血管生成作用与透明质酸(HA)结合无关,因为CD44HABD的非HA结合突变体仍保持抗血管生成特性。 本发明公开了基于血管细胞表面受体靶向的可溶性非糖基化CD44重组蛋白作为新一类血管生成抑制剂。 公开了使用重组CD44蛋白及其类似物阻断血管发生和治疗人类肿瘤的方法。 作为本发明的另一个实施方案,提出了使用CD44重组蛋白及其类似物筛选新药物靶标的方法。

    Molecules associated with the human suppressor of fused gene
    2.
    发明授权
    Molecules associated with the human suppressor of fused gene 失效
    与融合基因人抑制子相关的分子

    公开(公告)号:US06448020B1

    公开(公告)日:2002-09-10

    申请号:US09581831

    申请日:2000-08-21

    IPC分类号: G01N3353

    摘要: The present invention relates to proteins, polypeptides and nucleotides related to the human homologue of the Drosophila suppressor of fused gene, which is involved in the transduction of signals in the HH-PTC pathway. The invention also relates to antibodies raised against the polypeptides according to the invention. The molecules according to the present invention are useful in diagnostic and therapeutic methods relating to conditions associated with defects in said pathway, especially certain malformations and cancer. Other fields of application of the molecules according to the invention are e.g. studies of embryonic development, gene transcription and tissue repair.

    摘要翻译: 本发明涉及与融合基因的果蝇抑制因子的人类同源物有关的蛋白质,多肽和核苷酸,其涉及HH-PTC途径中的信号转导。 本发明还涉及针对根据本发明的多肽产生的抗体。 根据本发明的分子可用于涉及与所述途径中的缺陷相关的病症,特别是某些畸形和癌症的诊断和治疗方法。 根据本发明的分子的其它应用领域是例如。 胚胎发育,基因转录和组织修复研究。

    INHIBITION OR ACTIVATION OF SERINE/THREONINE ULK3 KINASE ACTIVITY
    6.
    发明申请
    INHIBITION OR ACTIVATION OF SERINE/THREONINE ULK3 KINASE ACTIVITY 审中-公开
    丝氨酸/螺旋体ULK3激酶活性的抑制或活化

    公开(公告)号:US20130040894A1

    公开(公告)日:2013-02-14

    申请号:US13500902

    申请日:2010-10-06

    CPC分类号: C12N9/1205 A61K48/00

    摘要: The present invention relates to human serine/threonine kinase ULK3 and its ability to regulate GLI transcription factors; mediators of SHH signaling. This disclosure demonstrates that ULK3 enhances endogenous and over-expressed GLI1 and GLI2 transcriptional activity in cultured cells, and ULK3 alters subcellular localization of GLI1. According to this disclosure ULK3 is an autophosphorylated kinase and phosphorylates GLI proteins in vitro. A peptide sequence in GLI1 C-terminus that is phosphorylated by ULK3 is provided in this disclosure. ULK3 catalytical activity is shown to be crucial for its function in SHH pathway. This disclosure shows that serine/threonine kinase ULK3 is involved in the SHH pathway as a positive regulator of GLI proteins. Furthermore, a therapeutic method in SHH dependent human disorders is disclosed by pharmacological inhibition of ULK3 kinase activity. Identification of ULK3 substrate sequence in GLI1 allows the design of peptide-based modulators of its kinase activity.

    摘要翻译: 本发明涉及人丝氨酸/苏氨酸激酶ULK3及其调节GLI转录因子的能力; SHH信号传导介质。 本公开表明ULK3增强培养细胞中内源性和过度表达的GLI1和GLI2转录活性,并且ULK3改变GLI1的亚细胞定位。 根据该公开内容,ULK3是一种自磷酸化激酶,并在体外磷酸化GLI蛋白。 在本公开中提供了通过ULK3磷酸化的GLI1 C-末端中的肽序列。 显示ULK3催化活性对其在SHH途径中的功能至关重要。 本公开显示丝氨酸/苏氨酸激酶ULK3作为GLI蛋白的阳性调节因子参与SHH途径。 此外,通过对ULK3激酶活性的药理学抑制来揭示SHH依赖性人类疾病中的治疗方法。 鉴定GLI1中的ULK3底物序列允许基于肽的调节剂设计其激酶活性。

    Drug for treating states related to the inhibition of angiogenesis and/or endothelial cell proliferation
    7.
    发明授权
    Drug for treating states related to the inhibition of angiogenesis and/or endothelial cell proliferation 失效
    用于治疗与抑制血管发生和/或内皮细胞增殖有关的状态的药物

    公开(公告)号:US08192744B2

    公开(公告)日:2012-06-05

    申请号:US12660886

    申请日:2010-03-05

    IPC分类号: A61K38/16 A61K39/00

    摘要: Soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in chick and mouse and thereby inhibits human tumor growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble non glycosylated CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumors using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues are presented.

    摘要翻译: 可溶性重组CD44透明质酸结合结构域(CD44HABD)抑制小鼠和小鼠的体内血管生成,从而抑制各种起源的人肿瘤生长。 CD44-HABD的抗血管生成作用与透明质酸(HA)结合无关,因为CD44HABD的非HA结合突变体仍保持抗血管生成特性。 本发明公开了基于血管细胞表面受体靶向的可溶性非糖基化CD44重组蛋白作为新一类血管生成抑制剂。 公开了使用重组CD44蛋白及其类似物阻断血管发生和治疗人类肿瘤的方法。 作为本发明的另一个实施方案,提出了使用CD44重组蛋白及其类似物筛选新药物靶标的方法。

    New drug
    8.
    发明申请
    New drug 审中-公开
    新药

    公开(公告)号:US20050054593A1

    公开(公告)日:2005-03-10

    申请号:US10487620

    申请日:2002-08-26

    摘要: CD44, the receptor for hyaluronic acid, has complex functions in cellular physiology, cell migration and tumour metastasis. The inventors have previously found that human CD44 receptor overexpression in mouse fibrosarcoma cells inhibits subcutaneous tumour growth in mice [Kogerman et al., Oncogene 1997; 15:1407-16; Kogerman et al., Clin Exp Metastasis 1998; 16:83-93]. Here it is demonstrated that a tumour growth inhibitory effect of CD44 is caused by block of angiogenesis. Furthermore, the inventors have found that soluble recombinant CD44 hyaluronic acid binding domain (CD44HABD) inhibits angiogenesis in vivo in cLick and mouse and thereby inhibits human tumour growth of various origins. The anti-angiogenic effect of CD44-HABD is independent of hyaluronic acid (HA) binding, since non-HA-binding mutants of CD44HABD still maintain anti-angiogenic properties. The invention discloses soluble CD44 recombinant proteins as a novel class of angiogenesis inhibitors based on targeting of vascular cell surface receptor. A method of block of angiogenesis and treatment of human tumours using recombinant CD44 proteins as well as their analogues is disclosed. As a further embodiment of the invention, methods for screening for new drug targets using CD44 recombinant proteins and their analogues is presented.

    摘要翻译: CD44是透明质酸的受体,在细胞生理学,细胞迁移和肿瘤转移中具有复杂的功能。 本发明人先前已经发现,小鼠纤维肉瘤细胞中的人CD44受体过表达抑制小鼠的皮下肿瘤生长[Kogerman等人,Oncogene 1997; 15:1407-16; Kogerman等人,Clin Exp Metastasis 1998; 16:83-93]。 这证明CD44的肿瘤生长抑制作用是由阻断血管生成引起的。 此外,本发明人已经发现可溶性重组CD44透明质酸结合结构域(CD44HABD)在cLick和小鼠体内抑制血管发生,从而抑制各种起源的人肿瘤生长。 CD44-HABD的抗血管生成作用与透明质酸(HA)结合无关,因为CD44HABD的非HA结合突变体仍保持抗血管生成特性。 本发明公开了基于血管细胞表面受体靶向的可溶性CD44重组蛋白作为新一类血管生成抑制剂。 公开了使用重组CD44蛋白及其类似物阻断血管发生和治疗人类肿瘤的方法。 作为本发明的另一个实施方案,提出了使用CD44重组蛋白及其类似物筛选新药物靶标的方法。