Identifying a novel anticancer agent with microtubule-stabilizing effects through computational cell-based bioactivity prediction models and bioassays
Identifying a novel anticancer agent with microtubule-stabilizing effects through computational cell-based bioactivity prediction models and bioassays
复制标题
通过基于计算的细胞生物活性预测模型和生物测定鉴定具有微管稳定作用的新型抗癌剂
DOI：
10.1039/c8ob02193g
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发表时间：
2019-02-14
影响因子：
3.2
通讯作者：
Wang, Ling
中科院分区：
文献类型：
--
作者：
Luo, Yao;Zeng, Ranran;Wang, Ling
我们报告通过建立基于计算抗癌细胞的模型鉴定了14种新的抗癌药物。其中，与fda批准的索拉非尼相比，化合物G03对MCF-7、HepG2、MDA-MB-231、HCTT116和HeLa的增殖抑制作用更强，IC50值分别为4.61、3.20、2.82、2.98和2.90 μ M。通过SPR、微管蛋白聚合、免疫荧光和western blot检测，证实该微管蛋白是G03的靶标。G03是一种结构简单的新型抗癌药物，具有独特的微管稳定作用。我们的研究展示了通过计算表型模型识别生物活性小分子，这代表了化学生物学和药物化学创新的可行途径。
We report the identification of 14 novel anticancer agents through established computational anticancer cell-based models. Among these novel hits, the compound G03 exhibits stronger inhibitory effects on the proliferation of MCF-7, HepG2, MDA-MB-231, HCTT116, and HeLa as compared with the FDA-approved sorafenib, with IC50 values of 4.61, 3.20, 2.82, 2.98, and 2.90 mu M, respectively. The tubulin protein was validated to be a target of G03 using SPR, tubulin polymerization, immunofluorescence, and western blot assays. G03 is a novel structurally simple anticancer agent with unusual microtubule-stabilizing effects. Our study demonstrated the identification of bioactive small molecules by computational phenotypic modeling, which represents a feasible route toward innovative leads for chemical biology and medicinal chemistry.