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

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2-Amino-2,3-dihydro-1H-indene-5-carboxamide-Based Discoidin Domain Receptor 1 (DDR1) Inhibitors: Design, Synthesis, and in Vivo Antipancreatic Cancer Efficacy.
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2019-08-02 , DOI: 10.1021/acs.jmedchem.9b00365
Dongsheng Zhu _{1,

2} , Huocong Huang ₃ , Daniel M Pinkas ₄ , Jinfeng Luo ₂ , Debolina Ganguly ₃ , Alice E Fox ₄ , Emily Arner ₃ , Qiuping Xiang ₂ , Zheng-Chao Tu ₂ , Alex N Bullock ₄ , Rolf A Brekken ₃ , Ke Ding ₁ , Xiaoyun Lu ₁

Affiliation

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.

中文翻译：

基于2-Amino-2,3-dihydro-1H-indene-5-carboxamide的Discoidin域受体1（DDR1）抑制剂：设计，合成和体内抗胰腺癌功效。

设计并合成了一系列2-氨基-2,3-二氢-1H-茚5羧酰胺作为新的选择性盘状结构域受体1（DDR1）抑制剂。代表性化合物之一7f与DDR1结合，其Kd值为5.9 nM，并以14.9 nM的一半最大（50％）抑制浓度值抑制了激酶活性。7f有效抑制胶原蛋白诱导的DDR1信号转导和上皮-间质转化，剂量依赖性地抑制胰腺癌细胞的集落形成，并且在胰腺癌的原位小鼠模型中显示出有希望的体内治疗功效。

更新日期：2019-07-16

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