2-Amino-2,3-dihydro-1 H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy

Dongsheng Zhu, Huocong Huang, Daniel M. Pinkas, Jinfeng Luo, Debolina Ganguly, Alice E. Fox, Emily Arner, Qiuping Xiang, Zheng Chao Tu, Alex N. Bullock, Rolf A. Brekken, Ke Ding, Xiaoyun Lu

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

A series of 2-amino-2,3-dihydro-1H-indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One of the representative compounds, 7f, bound with DDR1 with a Kd value of 5.9 nM and suppressed the kinase activity with an half-maximal (50%) inhibitory concentration value of 14.9 nM. 7f potently inhibited collagen-induced DDR1 signaling and epithelial-mesenchymal transition, dose-dependently suppressed colony formation of pancreatic cancer cells, and exhibited promising in vivo therapeutic efficacy in orthotopic mouse models of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)7431-7444
Number of pages14
JournalJournal of Medicinal Chemistry
Volume62
Issue number16
DOIs
StatePublished - Aug 22 2019

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Zhu, D., Huang, H., Pinkas, D. M., Luo, J., Ganguly, D., Fox, A. E., Arner, E., Xiang, Q., Tu, Z. C., Bullock, A. N., Brekken, R. A., Ding, K., & Lu, X. (2019). 2-Amino-2,3-dihydro-1 H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy. Journal of Medicinal Chemistry, 62(16), 7431-7444. https://doi.org/10.1021/acs.jmedchem.9b00365