一种新的MDM2-p53信号通路抑制剂的发现研究
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Q291

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国家自然基金(31401130)


Identification of a novel MDM2-p53 interaction inhibitor using virtual screening and docking strategy
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    摘要:

    本研究以研发新型小分子MDM2抑制剂为目的,建立了以分子对接为基础的虚拟筛选流程.利用虚拟筛选流程对SPECS化合物库的分子进行类药性筛选、分子对接粗筛、二次筛选以及排序挑选,并通过细胞实验验证这些分子激活p53并抑制肿瘤细胞生长的活性.结果表明M12能够激活p53及其下游信号通路,抑制肿瘤细胞周期并促进肿瘤细胞凋亡.M12与已知MDM2-p53抑制剂结构完全不同,是一种潜在的癌症治疗候选药物.

    Abstract:

    In this study we employed a docking approach based on virtual screening to search for inhibitors that can bind to MDM2 and block MDM2-p53 interaction. Candidate compounds were obtained from SPECS library. We processed two rounds of molecular docking. Putative compounds were selected based on binding score ranking and 3D structure inspection. Furthermore, the selected small molecules were validated by cell-based experiments. Treatment of several cancer cells with M12 led to activating p53, and upregulation of p21, leading to cell cycle arrest and apoptosis. To this end, we discovered a novel small molecule named M12 that is structurally different from the known MDM2 antagonists, M12 may be a novel small compound and a potentially useful drug candidate for cancer treatment.

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引用本文格式: 涂潇,李雷,张海波,刘扬,肖智雄,张渝君,曹洋. 一种新的MDM2-p53信号通路抑制剂的发现研究[J]. 四川大学学报: 自然科学版, 2019, 56: 369.

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历史
  • 收稿日期:2018-04-09
  • 最后修改日期:2018-04-25
  • 录用日期:2018-05-11
  • 在线发布日期: 2019-04-01
  • 出版日期: