Insights into the c-Jun N-terminal kinase 3 (JNK3) inhibitors: CoMFA, CoMSIA analyses and molecular docking studies

  • Yanda Liu
  • Yewei Xie
  • Yuanyuan Liu
  • Pengcheng Wang
  • Jiaxi Ye
  • Yalun Su
  • Zhihong Liang
  • Zhaohui He
  • Haibo Zhou
  • Guochao Liao
  • Jun Xu
  • Yiqun ChangEmail author
  • Pinghua SunEmail author
Original Research


JNK3, a protein kinase of the MAPK family that is potently activated by a variety of environmental stress and pro-inflammatory cytokines, has been recognized as an important therapeutic target for several neurodegenerative diseases. However, due to the long development cycle and the cost of R&D, no related drugs have been released. By applying the CoMFA and CoMSIA methods, QSAR models that explore the structure-activity relationship of the JNK3 inhibitors are established and validated, the parameters are satisfactory (q2 = 0.774, r2 = 0.991 for CoMFA model and q2 = 0.666, r2 = 0.990 for CoMSIA model) and base on which a series of novel molecules are designed. Molecular docking is conducted to verify the potential of the new compounds, the results shows promising activity. We speculated that the series of compounds S1S11 might have some therapeutic activity in the c-jnk3 pathway, particularly the “S8” may prove to be the best one, which provided useful guidance for the design of new and efficient subtype selective JNK3 inhibitors.


JNK3 Potential inhibitory activity QSAR Molecular docking 



This work was supported by the Natural Science Foundation of China (No. 81573294, 81773593, 81872759), the Excellent Young Teachers Program of Guangdong Provincial Colleges and Universities (YQ 2015061) and the Pearl River S&T Nova Program of Guangzhou (201610010100). We thank the software support from Dr. Junxia Zheng of the Guangdong University of Technology.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education, College of PharmacyJinan UniversityGuangzhouP. R. China
  2. 2.International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouChina
  3. 3.International Research Center of Medicinal AdministrationPeking UniversityBeijingP. R. China
  4. 4.Faculty of Medicine and Healththe University of SydneySydneyAustralia

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