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International Journal of Molecular Medicine
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Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening

  • Authors:
    • Nana Gao
    • Jixia Ren
    • Li Hou
    • Yue Zhou
    • Ling Xin
    • Jiedong Wang
    • Heming Yu
    • Yong Xie
    • Huiping Wang
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing 100038, P.R. China, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Haidian, Beijing 100193, P.R. China, Department of Reproductive Immunology and Pharamacology, National Research Institute for Family Planning, Beijing 100081, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 39-44
    |
    Published online on: May 23, 2016
       https://doi.org/10.3892/ijmm.2016.2602
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Abstract

Human testis-specific and bromodomain-containing protein (hBRDT) is essential for chromatin remodeling during spermatogenesis and is therefore an attractive target for the discovery of male contraceptive drugs. In this study, pharmacophore modeling was carried out based on the crystal structure of hBRDT in complex with the inhibitor, JQ1. The established pharmacophore model was used as a 3D search query to identify potent hBRDT inhibitors from an in-house chemical database. A molecular docking analysis was carried out to filter the obtained hit compounds. A total of 125 compounds was finally selected based on the ranking order and visual examination. These compounds were further evaluated by a protein-based in vitro assay. Four compounds with new chemical scaffolds were identified to be hBRDT inhibitors. The most active of these compounds, T480, had a half maximal inhibitory concentration (IC50) of 9.02 µM. The detailed analysis of the binding mode of compound T480 provides important information for the further development of novel BRDT inhibitors.
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Copy and paste a formatted citation
Spandidos Publications style
Gao N, Ren J, Hou L, Zhou Y, Xin L, Wang J, Yu H, Xie Y and Wang H: Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening. Int J Mol Med 38: 39-44, 2016.
APA
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J. ... Wang, H. (2016). Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening. International Journal of Molecular Medicine, 38, 39-44. https://doi.org/10.3892/ijmm.2016.2602
MLA
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J., Yu, H., Xie, Y., Wang, H."Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening". International Journal of Molecular Medicine 38.1 (2016): 39-44.
Chicago
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J., Yu, H., Xie, Y., Wang, H."Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening". International Journal of Molecular Medicine 38, no. 1 (2016): 39-44. https://doi.org/10.3892/ijmm.2016.2602
Copy and paste a formatted citation
x
Spandidos Publications style
Gao N, Ren J, Hou L, Zhou Y, Xin L, Wang J, Yu H, Xie Y and Wang H: Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening. Int J Mol Med 38: 39-44, 2016.
APA
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J. ... Wang, H. (2016). Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening. International Journal of Molecular Medicine, 38, 39-44. https://doi.org/10.3892/ijmm.2016.2602
MLA
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J., Yu, H., Xie, Y., Wang, H."Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening". International Journal of Molecular Medicine 38.1 (2016): 39-44.
Chicago
Gao, N., Ren, J., Hou, L., Zhou, Y., Xin, L., Wang, J., Yu, H., Xie, Y., Wang, H."Identification of novel potent human testis-specific and bromodomain-containing protein (BRDT) inhibitors using crystal structure-based virtual screening". International Journal of Molecular Medicine 38, no. 1 (2016): 39-44. https://doi.org/10.3892/ijmm.2016.2602
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