We describe a “phenotypic cell-binding screen” by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

中文翻译：

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表型细胞结合屏幕确定了靶向三阴性乳腺癌的新型化合物。

我们描述了一种“表型细胞结合筛选”，通过它可以在不了解药物靶标的情况下分离靶向特定表型的治疗性候选药物。在缺少目标表型的癌细胞存在下，将化学文库珠子与目标表型的癌细胞一起孵育，然后选择仅与目标表型的癌细胞结合的珠子作为命中。我们已将这种筛选策略应用于发现针对三阴性乳腺癌（TNBC）的新型化合物（LC129-8）。LC129-8在癌细胞系和患者来源的肿瘤组织中显示出与TNBC的高度特异性结合。LC129-8通过诱导凋亡，抑制增殖，逆转上皮-间质转化发挥抗TNBC活性，