TRPM2-specfic inhibitors
    3.
    发明申请
    TRPM2-specfic inhibitors 审中-公开
    TRPM2特异性抑制剂

    公开(公告)号:US20080114079A1

    公开(公告)日:2008-05-15

    申请号:US11652265

    申请日:2007-01-10

    CPC classification number: C07K14/705 A61K31/365 G01N33/6872 G01N2500/04

    Abstract: The present invention relates to methods and compositions for modulating ADPR-mediated migratory activity of cells through regulation of the TRPM2 cation channel. Such methods and compositions may be used for the treatment of disorders including, but not limited to, inflammation, ischemia, atherosclerosis, asthma, autoimmune disease, diabetes, arthritis, allergies, and transplant rejection. Such cells include, for example, neutrophils, lymphocytes, eosinophils, macrophages, monocytes and dendritic cells. The invention further relates to specific inhibition of TRPM2 by blocking the activity of ADPR. The invention also relates to drug screening assays designed to identify compounds that regulate TRPM2 and thereby also function to modulate ADPR-mediated cell migration. The invention is based on the discovery that, 8Br-ADPR, which specifically inhibits activation of TRPM2, acts to inhibit ADPR-mediated cell migration.

    Abstract translation: 本发明涉及通过调节TRPM2阳离子通道调节ADPR介导的细胞迁移活性的方法和组合物。 这些方法和组合物可用于治疗疾病,包括但不限于炎症,缺血,动脉粥样硬化,哮喘,自身免疫性疾病,糖尿病,关节炎,过敏反应和移植排斥。 这样的细胞包括例如嗜中性粒细胞,淋巴细胞,嗜酸性粒细胞,巨噬细胞,单核细胞和树突状细胞。 本发明还涉及通过阻断ADPR的活性而对TRPM2的特异性抑制。 本发明还涉及设计用于鉴定调节TRPM2的化合物并由此也可用于调节ADPR介导的细胞迁移的药物筛选测定。 本发明基于以下发现:特异性抑制TRPM2激活的8Br-ADPR起抑制ADPR介导的细胞迁移的作用。

Patent Agency Ranking