Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors

Zhen Wang, Yali Zhang, Sergio G. Bartual, Jinfeng Luo, Tingting Xu, Wenting Du, Qiuju Xun, Zhengchao Tu, Rolf A. Brekken, Xiaomei Ren, Alex N. Bullock, Guang Liang, Xiaoyun Lu, Ke Ding

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs). In addition, 7ae also exhibited promising in vivo anti-inflammatory effects in a LPS-induced mouse ALI model. To the best of our knowledge, this is the first “proof of concept” investigation on the potential application of a small molecule DDR1 inhibitor to treat ALI.

Original languageEnglish (US)
Pages (from-to)327-332
Number of pages6
JournalACS Medicinal Chemistry Letters
Issue number3
StatePublished - Mar 9 2017


  • DDR1
  • acute lung injury (ALI)
  • inflammation
  • inhibitor
  • structure−activity relationship (SAR)

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry


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