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三阴性乳腺癌是乳腺癌中最具侵略性的亚型,经常对化疗药物产生耐药性.靶向该肿瘤相关基因的G-四链体结构,有望开发出新的抗肿瘤药物.本研究靶向21-mer端粒G-四链体结构,通过基于结构的高通量虚拟筛选,得到可稳定端粒G-四链体的化合物VB07和VC02.细胞毒性实验表明,VB07和VC02在5μM的浓度下对三阴性乳腺癌细胞具有抑制作用.这项研究表明基于结构的高通量虚拟筛选可以成功地发现靶向端粒G-四链体的化合物,并利用此方法发现可抑制三阴性乳腺癌细胞的新化合物.“,”Triple-negative breast cancer is an aggressive subtype that frequently develops resistance to chemotherapy.It is expected to develop new anti-tumor drugs through targeting the structure of G-quadruplexes of the genes associated with this tumor.In this work,by targeting the 21-mer telomere G-quadruplex structure,compounds VB07 and VC02 were identified to stabilize the telomere G-quadruplex through structure-based high-throughput virtual screening.Cell cytotoxicity assay showed that VB07 and VC02 exhibited inhibitory effect on triple-negative breast cancer cells at the concentration of 5 μM.This study showed that structure-based high-throughput virtual screening was able to successfully identify the proper compounds targeting the telomere G-quadruplex,which exhibited inhibitory effects against the triple-negative breast cancer cells.