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Identification of protein arginine methyltransferase 7 (PRMT7) inhibitor by virtual screening and biological evaluation in vitro

  • Linlin Liu
  • Xiaoning Kai
  • Qingqing Chen
  • Ling Zhang
  • Ruosi YaoEmail author
  • Jian GaoEmail author
Original Research
  • 68 Downloads

Abstract

Although protein arginine methyltransferase 7 (PRMT7) is an important mediator in various biological processes, its specific inhibitors remain to be identified. To identify novel inhibitors of PRMT7, we utilized high-throughput virtual screening of the ChemDiv database for novel PRMT7 inhibitors. Eight compounds were identified, and among them, compound V009-0749 exhibited potent anticancer activity against the HepG2 hepatocellular carcinoma cell line in a dose-dependent manner. It inhibited the activity of PRMT7 by decreasing the histone H4 Arg 3 symmetric dimethylation (H4R3me2s) modification level in the HepG2 and Hep3B carcinoma cell lines. Furthermore, compound V009-0749 led to HepG2 and Hep3B cell cycle G1 phase arrest and cell apoptosis. Molecular modeling studies also suggested that compound V009-0749 had strong affinity for the binding site of PRMT7 by forming six hydrogen bonds and significant hydrophobic interactions. Compound V009-0749 could serve as a lead compound targeting PRMT7 activity, and lay the foundation for investigating the role of PRMT7 in hepatocellular carcinoma and other diseases.

Keywords

Virtual screening PRMT7 Proliferation Hepatocellular carcinoma 

Notes

Acknowledgements

This study was funded by National Natural Science Foundation of China (Grant No. 21708033, 81600173), Natural Science Foundation of Jiangsu Province (Grant No. BK20160230), Science and Technology Project of Xuzhou City (Grant No. KC16SG249), Scientific Research Foundation for Talented Scholars of Xuzhou Medical University (Grant No. D2014008), Postdoctoral Science Foundation of China (Grant No. 2018T110554), and Natural Science Foundation of the Jiangsu Higher Education Institutions of China (Grant No. 18KJB416008).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2270_MOESM1_ESM.doc (2.1 mb)
Supplementary Information

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Jiangsu Key Laboratory of New Drug Research and Clinical PharmacyXuzhou Medical UniversityXuzhouP. R. China
  2. 2.College of Medical ImagingXuzhou Medical UniversityXuzhouChina
  3. 3.Blood Diseases InstituteXuzhou Medical UniversityXuzhouChina
  4. 4.Department of HematologyThe Affliated Hospital of Xuzhou Medical UniversityXuzhouChina

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