2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.
J Med Chem
; 62(16): 7431-7444, 2019 08 22.
Article
em En
| MEDLINE
| ID: mdl-31310125
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Ensaios Antitumorais Modelo de Xenoenxerto
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Receptor com Domínio Discoidina 1
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Neoplasias Experimentais
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Antineoplásicos
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article