DNA修复
DNA
同源重组
分子动力学
化学
癌症研究
计算生物学
生物物理学
分子模型
动力学(音乐)
DNA损伤修复
药品
信号转导衔接蛋白
分子探针
结合位点
血浆蛋白结合
生物化学
细胞生物学
结构-活动关系
雷达51
体外
DNA损伤
抗药性
生物活性
同源染色体
平方毫米
HEK 293细胞
作者
Leyuan Chen,Gaiting Liu,Fancui Meng,Yu Shi,Zhennan Fang,Zhenyu Peng,M Wang,Wenfeng Gou,Wenbin Hou,Yiliang Li
摘要
Abstract DNA repair is strongly associated with tumor resistance to radiotherapy and chemotherapy. WD repeat and HMG‐box DNA binding protein 1 (WDHD1) is a key adaptor for homologous recombination repair of DNA, and its overexpression is relevant to the poor prognosis of many tumor patients. We previously have identified and validated bazedoxifene (BZA), which had 60% inhibitory rate on WDHD1 in MCF7 cells at 10 μM, from the Food and Drug Administration‐approved compound library. Here, we initially established the binding model of BZA, synthesized and evaluated eight BZA analogs. Further, we detailed the use of molecular dynamics simulations to provide insights into the basis for activity against WDHD1. This binding mode will be instructive for the development of new WDHD1 degraders.
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