Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure
Virtual screening for triple-negative breast cancer cell inhibitors based on telomere G-quadruplex structure
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基于端粒G-四链体结构的三阴性乳腺癌细胞抑制剂虚拟筛选
DOI：
10.5246/jcps.2020.06.036
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发表时间：
2020-06
影响因子：
--
通讯作者：
Sisi Liu
中科院分区：
文献类型：
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作者：
Hua Deng;Chao Gao;Dengguo Wei;Sisi Liu
三阴性乳腺癌是一种侵袭性亚型，经常对化疗产生耐药性。以肿瘤相关基因的G-四链体结构为靶点，有望开发新的抗肿瘤药物。在这项工作中，通过靶向21-mer端粒G-四链体结构，化合物VB 07和VC 02通过基于结构的高通量虚拟筛选被鉴定为稳定端粒G-四链体。细胞毒性试验表明，VB 07和VC 02在5 μM浓度下对三阴性乳腺癌细胞有抑制作用。这项研究表明，基于结构的高通量虚拟筛选能够成功地识别出靶向端粒G-四链体的合适化合物，这些化合物对三阴性乳腺癌细胞具有抑制作用。
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.