三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，因为治疗选择有限，预后更为不良，复发的概率更高。鉴定和测试TNBC治疗的潜在治疗靶点至关重要。利用从基因表达 Omnibus 收集的三阴性乳腺癌的转录标志，我们利用 CMap 重新定位化合物以治疗TNBC。进行CCK8和胶落形成实验以检测候选药物对TNBC细胞增殖的影响。同时，实施细胞转移和伤口愈合实验以检测候选药物引起的细胞转移变化。此外，目前正在进行蛋白质组学方法以评估候选药物在TNBC中的作用机制。此外，药物亲和力响应目标稳定性（DARTS）结合 LC-MS/MS 进行，以探究 TNBC 细胞中的潜在药物靶标。我们发现，最广泛使用的药物之一，丁香酚，可以减少TNBC细胞的生长和转移。根据蛋白组学揭示的潜在机制，丁香酚可通过 NOD1-NF-κB 信号通路抑制TNBC细胞的增殖和转移。DARTS实验进一步揭示，丁香酚可能与TNBC细胞中的NF-κB结合。我们的研究结果指出，丁香酚是TNBC治疗的潜在候选药物。版权所有©2023 Shi, Zhang, Bao, Liu, Yang 和 Yin。

The most aggressive subtype of breast cancer, triple-negative breast cancer (TNBC), has a worse prognosis and a higher probability of relapse since there is a narrow range of treatment options. Identifying and testing potential therapeutic targets for the treatment of TNBC is of high priority.Using a transcriptional signature of triple-negative breast cancer collected from Gene Expression Omnibus (GEO), CMap was utilized to reposition compounds for the treatment of TNBC. CCK8 and colony formation experiments were performed to detect the effect of the candidate drug on the proliferation of TNBC cells. Meanwhile, transwell and wound healing assay were implemented to detect cell metastasis change caused by the candidate drug. Moreover, the proteomic approach was presently ongoing to evaluate the underlying mechanism of the candidate drug in TNBC. Furthermore, drug affinity responsive target stability (DARTS) coupled with LC-MS/MS was carried out to explore the potential drug target candidate in TNBC cells.We found that the most widely used medication, eugenol, reduced the growth and metastasis of TNBC cells. According to the underlying mechanism revealed by proteomics, eugenol could inhibit TNBC cell proliferation and metastasis via the NOD1-NF-κB signaling pathway. DARTS experiment further revealed that eugenol may bind to NF-κB in TNBC cells.Our findings pointed out that eugenol was a potential candidate drug for the treatment of TNBC.Copyright © 2023 Shi, Zhang, Bao, Liu, Yang and Yin.