三陰性乳腺癌是乳腺癌中最具侵略性的亞型,經(jīng)常對化療藥物產(chǎn)生耐藥性。靶向該腫瘤相關(guān)基因的G-四鏈體結(jié)構(gòu),有望開發(fā)出新的抗腫瘤藥物。本研究靶向21-mer端粒G-四鏈體結(jié)構(gòu),通過基于結(jié)構(gòu)的高通量虛擬篩選,得到可穩(wěn)定端粒G-四鏈體的化合物VB07和VC02。細胞毒性實驗表明,VB07和VC02在5μM的濃度下對三陰性乳腺癌細胞具有抑制作用。這項研究表明基于結(jié)構(gòu)的高通量虛擬篩選可以成功地發(fā)現(xiàn)靶向端粒G-四鏈體的化合物,并利用此方法發(fā)現(xiàn)可抑制三陰性乳腺癌細胞的新化合物。 

【文章來源】：Journal of Chinese Pharmaceutical Sciences. 2020,29(06)CSCD

【文章頁數(shù)】：7 頁

【文章目錄】：
1. Introduction
2. Material and methods
    2.1. Materials
    2.2. Structure-based high-throughput virtual screening
    2.3. FRET assay
    2.4. Cell cytotoxicity assay
3. Results and discussion
    3.1. Structure-based virtual screening for telomere G-quadruplex ligands
    3.2. VB07 shows high stabilization ability for the telomere G-quadruplex
    3.3. Binding mode prediction of telomere G-quadruplex and candidate compounds by molecular docking
    3.4. VB07 and VC02 inhibit proliferation of breast cancer cells
4. Conclusions



本文編號：3380541