Bromodomain is a recognition module in the signal transduction of acetylated histone. BRD4, one of the bromodomain members, is emerging as an attractive therapeutic target for several types of cancer. Therefore, in this study, an attempt has been made to screen compounds from an integrated database containing 5.5 million compounds for BRD4 inhibitors using pharmacophore‐based virtual screening, molecular docking, and molecular dynamics simulations. As a result, two molecules of twelve hits were found to be active in bioactivity tests. Among the molecules, compound 5 exhibited potent anticancer activity, and the IC₅₀ values against human cancer cell lines MV4‐11, A375, and HeLa were 4.2, 7.1, and 11.6 μm, respectively. After that, colony formation assay, cell cycle, apoptosis analysis, wound‐healing migration assay, and Western blotting were carried out to learn the bioactivity of compound 5.

中文翻译：

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基于药理学的虚拟筛选，分子对接，分子动力学模拟和生物学评估，用于发现新型BRD4抑制剂

Bromodomain是乙酰化组蛋白信号转导中的识别模块。BRD4是一种溴结构域成员，正在成为多种类型癌症的有吸引力的治疗靶标。因此，在这项研究中，我们尝试使用基于药效团的虚拟筛选，分子对接和分子动力学模拟，从包含550万种BRD4抑制剂化合物的综合数据库中筛选化合物。结果，发现十二个命中的两个分子在生物活性测试中具有活性。间的分子，化合物5显示出强效的抗癌活性，并且IC ₅₀对人癌症细胞系MV4-11，A375，和HeLa值分别为4.2，7.1和11.6μ米， 分别。之后，进行集落形成测定，细胞周期，凋亡分析，伤口愈合迁移测定和蛋白质印迹，以了解化合物5的生物活性。