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 language | English (US) |
|---|---|
| Journal | Journal of Medicinal Chemistry |
| DOIs | |
| State | Accepted/In press - Jan 1 2019 |
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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 journal › Article
}
TY - JOUR
T1 - 2-Amino-2,3-dihydro-1 H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors
T2 - Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy
AU - Zhu, Dongsheng
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
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070703912&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070703912&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.9b00365
DO - 10.1021/acs.jmedchem.9b00365
M3 - Article
C2 - 31310125
AN - SCOPUS:85070703912
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
ER -