Combined pharmacophore models as virtual screening protocol against BRD4(1) inhibitor

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• 作者：Yifei Yang ; Fangxia Zou ; Leilei Zhao ; Yulan Cheng…
• 关键词：BRD4(1) inhibitors ; Combined pharmacophore ; Cancer ; Docking ; Virtual screening
• 刊名：Medicinal Chemistry Research
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：25
• 期：4
• 页码：585-595
• 全文大小：1,676 KB
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• 作者单位：Yifei Yang (1)
  Fangxia Zou (2) (3) (4)
  Leilei Zhao (5)
  Yulan Cheng (1)
  Xiaoming Zha (2) (3) (4)
  Huibin Zhang (5)
  Jinpei Zhou (1)
  
  1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China
  2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China
  3. Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, People’s Republic of China
  4. Department of Biomedical Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China
  5. Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China
  
• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Cell Biology;
• 出版者：Springer US
• ISSN：1554-8120

文摘

Bromodomain-containing protein is involved in many essential cellular processes, such as chromosomes for cell cycle progression, cellular viability and embryonic stem cell regulation, which plays a significant role in cancers and lysine acetylation. However, there is no information available regarding the discovery for structurally novel existing BRD4(1) inhibitors up to date. Therefore, we collected reported compounds from GSK library to generate ligand-based pharmacophore and used 11 BRD4(1)-inhibitor co-crystal structures to establish our structure-based pharmacophore for multiple virtual screening of potent BRD4(1) inhibitors. These results may provide important information for further design and optimization of novel BRD4(1) inhibitors in cancer treatment. The results of this study will not only provide a better understanding of BRD4(1) inhibitors interaction, but will also assist the development of new potent hits for BRD4(1).