Organometallic metal(arene) anticancer agents require ligand exchange for their anticancer activity and this is generally believed to confer low selectivity for potential cellular targets. However, using an integrated proteomics‐based target‐response profiling approach as a potent hypothesis‐generating procedure, we found an unexpected target selectivity of a ruthenium(arene) pyridinecarbothioamide (plecstatin) for plectin, a scaffold protein and cytolinker, which was validated in a plectin knock‐out model in vitro. Plectin targeting shows potential as a strategy to inhibit tumor invasiveness as shown in cultured tumor spheroids while oral administration of plecstatin‐1 to mice reduces tumor growth more efficiently in the invasive B16 melanoma than in the CT26 colon tumor model.

中文翻译：

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有机钌抗癌剂对Plectin表现出意外的目标选择性

有机金属金属（芳烃）抗癌剂需要交换配体才能发挥其抗癌活性，通常认为这对潜在的细胞靶标具有低选择性。但是，使用基于蛋白质组学的靶标-响应分析综合方法作为有效的假设生成程序，我们发现钌（芳烃）吡啶碳硫代酰胺（plecstatin）的目标选择性出乎意料地选择了凝集素，支架蛋白和细胞连接剂，并在以下方法中进行了验证体外选择凝集素的基因敲除模型。如在培养的肿瘤球体中所示，血凝素靶向显示出一种潜在的抑制肿瘤侵袭性的策略，而对小鼠口服plecstatin-1则在侵袭性B16黑色素瘤中比在CT26结肠肿瘤模型中更有效地降低了肿瘤的生长。