雷达51
重组酶
同源重组
化学
癌症研究
癌症
癌细胞
三阴性乳腺癌
细胞生长
乳腺癌
药理学
DNA
生物
生物化学
遗传学
重组
基因
作者
Jiewen Zhu,Hong‐Yuan Chen,Xuning Emily Guo,Xiao‐Long Qiu,Chunmei Hu,A. Richard Chamberlin,Wen‐Hwa Lee
标识
DOI:10.1016/j.ejmech.2015.04.021
摘要
RAD51 recombinase plays a critical role for cancer cell proliferation and survival. Targeting RAD51 is therefore an attractive strategy for treating difficult-to-treat cancers, e.g. triple negative breast cancers which are often resistant to existing therapeutics. To this end, we have designed, synthesized and evaluated a panel of new RAD51 inhibitors, denoted IBR compounds. Among these compounds, we have identified a novel small molecule RAD51 inhibitor, IBR120, which exhibited a 4.8-fold improved growth inhibition activity in triple negative human breast cancer cell line MBA-MD-468. IBR120 also inhibited the proliferation of a broad spectrum of other cancer cell types. Approximately 10-fold difference between the IC50 values in normal and cancer cells were observed. Moreover, IBR120 was capable of disrupting RAD51 multimerization, impairing homologous recombination repair, and inducing apoptotic cell death. Therefore, these novel RAD51 inhibitors may serve as potential candidates for the development of pharmaceutical strategies against difficult-to-treat cancers.
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