2. Academic Validation
  3. Design, synthesis, and structure activity relationship (SAR) studies of novel imidazo[1,2-a] pyridine derivatives as Nek2 inhibitors

Design, synthesis, and structure activity relationship (SAR) studies of novel imidazo[1,2-a] pyridine derivatives as Nek2 inhibitors

  • Bioorg Med Chem. 2020 Dec 1;28(23):115775. doi: 10.1016/j.bmc.2020.115775.
Haili Wang 1,  Yunzhong Chen 1,  Xiaofan Gu 1,  Jianbei Xi 1,  Ziwei Ren 1,  Shuting Wang 1,  Yanhong Duan 2,  Hongyu Li 3,  Tong Zhu 1,  Yijie Du 4,  Xiongwen Zhang 5,  Mingliang Ma 6
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
  • 2 Key Laboratory of Brain Functional Genomics-Ministry of Education, School of Life Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, China.
  • 3 Department of Pharmaceutical Science, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
  • 4 Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai 200040, China. Electronic address: [email protected].
  • 5 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China. Electronic address: [email protected].
  • 6 Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China; Key Laboratory of Brain Functional Genomics-Ministry of Education, School of Life Science, East China Normal University, 3663 North Zhongshan Road, Shanghai, China. Electronic address: [email protected].
PMID: 32992252 DOI: 10.1016/j.bmc.2020.115775
Abstract

Never in mitosis (NIMA) related kinase 2 (Nek2) is involved in multiple cellular processes such as cell cycle checkpoint regulation, cell division, DNA damage response and cell Apoptosis. Nek2 has been reported to be overexpressed in various tumors and correlated with poor prognosis. Herein, a series of imidazo[1,2-a] pyridines Nek2 inhibitors were designed, synthesized, and their biological activities were investigated. Besides, structure activity relationship analysis of these compounds were performed in the MGC-803 cell. The screening results are promising, and compound 28e shows good proliferation inhibitory activity with an IC50 of 38 nM. The results would be helpful to design and develop more effective Nek2 inhibitors for the treatment of gastric Cancer.

Keywords

Antitumor activities; Gastric cancer; Imidazo[1,2-a]pyridine; Nek2.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-150046
    Nek2 Inhibitor