We synthesized affinity-based chemical probes of cytosine-adenosine bisubstrate analogs and identified several potential targets by proteomic analysis. The validation of the proteomic analysis identified the chemical probe as a specific inhibitor of glucose-regulated protein 94 (GRP94), a potential drug target for several types of cancers. Therefore, as a result of the use of bisubstrate-type chemical probes and a chemical-biology methodology, this work opens the way to the development of a new family of GRP94 inhibitors that could potentially be of therapeutic interest.

中文翻译：

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双底物型化学探针将GRP94鉴定为含胞嘧啶腺苷类似物的潜在靶标。

我们合成了基于亲和力的化学探针的胞嘧啶-腺苷双底物类似物，并通过蛋白质组学分析确定了几个潜在的目标。蛋白质组学分析的有效性确定了该化学探针是葡萄糖调节蛋白94（GRP94）的特异性抑制剂，该蛋白是多种类型癌症的潜在药物靶标。因此，由于使用了双底物型化学探针和化学生物学方法，这项工作为开发可能具有治疗意义的新的GRP94抑制剂家族开辟了道路。