Modulation of biological signal transduction by RNA interference
    53.
    发明申请
    Modulation of biological signal transduction by RNA interference 失效
    通过RNA干扰调节生物信号转导

    公开(公告)号:US20040077574A1

    公开(公告)日:2004-04-22

    申请号:US10444795

    申请日:2003-05-23

    申请人: CEPTYR, Inc.

    摘要: Compositions and methods relating to small interfering RNA (siRNA) polynucleotides are provided as pertains to modulation of biological signal transduction. Shown are siRNA polynucleotides that interfere with expression of members of the protein tyrosine phosphatase (PTP) class of enzymes that mediate signal transduction, and with certain MAP kinase kinases (MKK). In certain preferred embodiments siRNA modulate signal transduction pathways comprising SHP2, cdc14a/b, cdc25A/B/C, KAP, PTP-null, PRL-3, CD45, dual specificity phosphatase-3 (DSP-3), MKK-4, and/or MKK-7. Modulation of PTP-mediated biological signal transduction has uses in diseases associated with defects in cell proliferation, cell differentiation and/or cell survival, such as metabolic disorders (including diabetes and obesity), cancer, autoimmune disease, infectious and inflammatory disorders and other conditions. The invention also provides siRNA polynucleotides that interfere with expression of chemotherapeutic target polypeptides, such as DHFR, thymidylate synthetase, and topoisomerase I.

    摘要翻译: 提供了与小干扰RNA(siRNA)多核苷酸相关的组合物和方法,涉及生物信号转导的调节。 显示干扰介导信号转导的酶的蛋白酪氨酸磷酸酶(PTP)类成员和某些MAP激酶激酶(MKK)的成员的表达的siRNA多核苷酸。 在某些优选实施方案中,siRNA调节包含SHP2,cdc14a / b,cdc25A / B / C,KAP,PTP-ε,PRL-3,CD45,双特异性磷酸酶-3(DSP-3),MKK-4和 /或MKK-7。 PTP介导的生物信号转导的调节在与细胞增殖,细胞分化和/或细胞存活缺陷相关的疾病中使用,例如代谢紊乱(包括糖尿病和肥胖症),癌症,自身免疫性疾病,感染性和炎症性疾病和其他病症 。 本发明还提供干扰化学治疗靶多肽如DHFR,胸苷酸合成酶和拓扑异构酶I的表达的siRNA多核苷酸。

    Therapeutic compositions comprised of pentamidine and methods of using same to treat cancer
    55.
    发明申请
    Therapeutic compositions comprised of pentamidine and methods of using same to treat cancer 审中-公开
    由戊脒组成的治疗组合物及其使用方法治疗癌症

    公开(公告)号:US20040010045A1

    公开(公告)日:2004-01-15

    申请号:US10427887

    申请日:2003-05-01

    发明人: Taolin Yi

    IPC分类号: A61K031/155

    摘要: Pentamidine, an anti-protozoa drug, is described herein as a potent PTPase inhibitor with anti-cancer activity. Pentamidine at its therapeutic doses inhibits recombinant PRL phosphatases and inactivates intracellular PRLs in NIH3T3 transfectants. Pentamidine treatment at a nontoxic dose markedly inhibits the growth of WM9 human melanoma tumors in nude mice coincident with tumor cell necrosis and is capable of inactivating an ectopically expressed PRL-2 in the cancer cells. The drug has growth inhibitory activity against different human cancer cell lines that express the PRLs, and therefore has broad anti-cancer activity based on inactivating the oncogenic phosphatases.

    摘要翻译: 戊脒是抗原生动物药物,在本文中被描述为具有抗癌活性的有效的PTPase抑制剂。 Pentamidine在其治疗剂量下抑制重组PRL磷酸酶,并使NIH3T3转染子中的细胞内PRL失活。 在无毒剂量下的戊脒处理显着抑制与肿瘤细胞坏死相符的裸小鼠中WM9人黑素瘤肿瘤的生长,并且能够灭活癌细胞中异位表达的PRL-2。 该药物对表达PRL的不同人类癌细胞系具有生长抑制活性,因此具有广泛的抗癌活性,其基于致死性致癌性磷酸酶的失活。

    DSP-9 dual-specificity phosphatase
    58.
    发明申请
    DSP-9 dual-specificity phosphatase 审中-公开
    DSP-9双特异性磷酸酶

    公开(公告)号:US20030119045A1

    公开(公告)日:2003-06-26

    申请号:US10314058

    申请日:2002-12-05

    申请人: Ceptyr, Inc.

    发明人: Ralf M. Luche Bo Wei

    摘要: Compositions and methods are provided for the treatment of conditions associated with cell proliferation, cell differentiation and cell survival. In particular, the dual-specificity phosphatase DSP-9, and polypeptide variants thereof that stimulate dephosphorylation of DSP-9 substrates, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit DSP-9 activity. The polypeptides and agents may be used to modulate cell proliferation, differentiation and survival.

    摘要翻译: 提供组合物和方法用于治疗与细胞增殖,细胞分化和细胞存活相关的病症。 特别地,提供了刺激DSP-9底物去磷酸化的双重特异性磷酸酶DSP-9及其多肽变体。 多肽可用于例如鉴定抑制DSP-9活性的抗体和其它试剂。 多肽和试剂可用于调节细胞增殖,分化和存活。