Design and Optimization of 3′-(Imidazo[1,2-a]pyrazin-3-yl)-[1,1′-biphenyl]-3-carboxamides as Selective DDR1 Inhibitors

Cheng Mo, Zhang Zhang, Yupeng Li, Minhao Huang, Jian Zou, Jinfeng Luo, Zheng-Chao Tu, Yong Xu, Xiaomei Ren, Ke Ding, Xiaoyun Lu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3′-(imidazo[1,2-a]pyrazin-3-yl)-[1,1′-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound 8v potently inhibited DDR1 with an IC 50 of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC 50 = 1740 nM) and negligible activities against Bcr-Abl (IC 50 > 10 μM) and c-Kit (IC 50 > 10 μM). 8v also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.

Original languageEnglish
Pages (from-to)379-384
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number3
StatePublished - Mar 12 2020

Bibliographical note

Funding Information:
This work was supported by National Natural Science Foundation of China (81922062, 81874285, and 81820108029), National Key Research and Development Program of China (218YFE0105800), and Guangdong Province Science and Technology Program (2018A050506043) and Jinan University.

Publisher Copyright:
Copyright © 2020 American Chemical Society.


  • DDR1
  • SAR
  • drug discovery
  • selective inhibitor

PubMed: MeSH publication types

  • Journal Article


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