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

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)
JournalJournal of Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 1 2019

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Pancreatic Neoplasms
Neoplasms
Epithelial-Mesenchymal Transition
Inhibitory Concentration 50
Phosphotransferases
Collagen
indene
Discoidin Domain Receptor 1
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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

In: Journal of Medicinal Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

Zhu, Dongsheng ; Huang, Huocong ; Pinkas, Daniel M. ; Luo, Jinfeng ; Ganguly, Debolina ; Fox, Alice E. ; Arner, Emily ; Xiang, Qiuping ; Tu, Zheng Chao ; Bullock, Alex N. ; Brekken, Rolf A ; Ding, Ke ; Lu, Xiaoyun. / 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. In: Journal of Medicinal Chemistry. 2019.
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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.",
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AU - Huang, Huocong

AU - Pinkas, Daniel M.

AU - Luo, Jinfeng

AU - Ganguly, Debolina

AU - Fox, Alice E.

AU - Arner, Emily

AU - Xiang, Qiuping

AU - Tu, Zheng Chao

AU - Bullock, Alex N.

AU - Brekken, Rolf A

AU - Ding, Ke

AU - Lu, Xiaoyun

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