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    • 7. 发明申请
    • Radiolabeled Inhibitors of the Amino Acid Transporters ASCT1 and ASCT2
    • 氨基酸转运蛋白ASCT1和ASCT2的放射性标记抑制剂
    • US20150056138A1
    • 2015-02-26
    • US14515103
    • 2014-10-15
    • Stephanie Lynn Martinelli
    • Christopher Sean EsslingerMichael P. KavanaughBrent LydaNicholas R. Natale
    • A61K51/04C07D207/16
    • C07D207/16A61K51/0446C07B59/002
    • The invention features compounds and methods relating to hydroxy-proline analog inhibitors of the ASCT1 and ASCT2 neutral amino acid transporters useful for diagnostic purposes. These analogs are potent and selective inhibitors of ASCT2 and ASCT1-mediated amino acid transport as evidenced by significantly reduced glutamine or alanine transport-associated currents or radiolabeled substrate (amino acid) uptake in Xenopus oocytes expressing ASCT2 or ASCT1. Selectivity has been established in the same manner whereby reduced substrate associated current or substrate uptake is unobserved in Xenopus oocytes expressing ATA2, SN1, or EAAT(s) (excitatory amino acid transporter). The compounds and methods of the invention include radiolabeled inhibitors that can be used in research or clinical applications (e.g., for the treatment of cancer or ischemia-related central nervous system injury).
    • 本发明涉及可用于诊断目的的ASCT1和ASCT2中性氨基酸转运蛋白的羟基 - 脯氨酸类似物抑制剂的化合物和方法。 这些类似物是ASCT2和ASCT1介导的氨基酸转运的有效和选择性抑制剂,通过在表达ASCT2或ASCT1的非洲爪蟾卵母细胞中显着降低谷氨酰胺或丙氨酸转运相关电流或放射性标记的底物(氨基酸)摄取来证明。 选择性已经以相同的方式建立,从而在表达ATA2,SN1或EAAT(兴奋性氨基酸转运蛋白)的非洲爪蟾卵母细胞中不能观察到减少的底物相关电流或底物摄取。 本发明的化合物和方法包括可用于研究或临床应用的放射性标记的抑制剂(例如,用于治疗癌症或缺血相关的中枢神经系统损伤)。