Structure-based design and synthesis of imidazo[1,2-a]pyridine derivatives as novel and potent Nek2 inhibitors with in vitro and in vivo antitumor activities

Jian Bei Xi, Yan Fen Fang, Brendan Frett, Meng Li Zhu, Tong Zhu, Yan Nan Kong, Feng Jie Guan, Yun Zhao, Xiong Wen Zhang, Hong Yu Li, Ming Liang Ma, Wenhao Hu

Research output: Contribution to journalArticle

12 Scopus citations


We present herein the discovery and development of novel and potent Nek2 inhibitors with distinctive in vitro and in vivo antitumor activity based on an imidazo[1,2-a]pyridine scaffold. Our studies identified a nonlinear SAR for activity against both Nek2 and cancer cells. Bioisostere and structure-based design techniques were employed to identify compounds 42c (MBM-17, IC50 = 3.0 nM) and 42g (MBM-55, IC50 = 1.0 nM), which displayed low nanomolar activity and excellent selectivity for Nek2. Both compounds effectively inhibited the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. Importantly, the salts form of these two compounds (MBM-17S and MBM-55S) significantly suppressed tumor growth in vivo without apparent toxicity based on appearance and changes in body weight. In summary, MBM-17 and MBM-55 displayed the potential for substantial therapeutic application in cancer treatment.

Original languageEnglish (US)
Pages (from-to)1083-1106
Number of pages24
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Jan 27 2017
Externally publishedYes



  • Antitumor activity
  • Imidazo[1,2-a]pyridine
  • Nek2 inhibitors
  • Selectivity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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