A novel strategy to attach indole‐containing payloads to antibodies through a carbamate moiety and a self‐immolating, disulfide‐based linker is described. This new strategy was employed to connect a selective estrogen receptor down‐regulator (SERD) to various antibodies in a site‐selective manner. The resulting conjugates displayed potent, antigen‐dependent down‐regulation of estrogen receptor levels in MCF7‐neo/HER2 and MCF7‐hB7H4 cells. They also exhibited similar antigen‐dependent modulation of the estrogen receptor in tumors when administered intravenously to mice bearing MCF7‐neo/HER2 tumor xenografts. The indole‐carbamate moiety present in the new linker was stable in whole blood from various species and also exhibited good in vivo stability properties in mice.

中文翻译：

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通过新型自消灭连接子将吲哚与抗体结合

描述了一种通过氨基甲酸酯部分和基于自硫化的，基于二硫键的连接子将含吲哚的有效载荷附着于抗体的新策略。采用这种新策略可以将位点选择性雌激素受体下调剂（SERD）连接到各种抗体。产生的结合物在MCF7-neo / HER2和MCF7-hB7H4细胞中显示出强大的，依赖抗原的雌激素受体水平下调。当向带有MCF7-neo / HER2肿瘤异种移植物的小鼠静脉内给药时，它们还表现出相似的抗原依赖性肿瘤中雌激素受体的调节作用。新接头中存在的吲哚氨基甲酸酯部分在各种物种的全血中稳定，并且在小鼠中也表现出良好的体内稳定性。