@article{8fc7b14ae64e47af832cf4bc0daa7f0d,
title = "Tetrahydroisoquinoline-7-carboxamide Derivatives as New Selective Discoidin Domain Receptor 1 (DDR1) Inhibitors",
abstract = "Acute lung injury (ALI) is a deadly symptom for serious lung inflammation. Discoidin Domain Receptor 1 (DDR1) is a new potential target for anti-inflammatory drug discovery. A new selective tetrahydroisoquinoline-7-carboxamide based DDR1 inhibitor 7ae was discovered to tightly bind the DDR1 protein and potently inhibit its kinase function with a Kd value of 2.2 nM and an IC50 value of 6.6 nM, respectively. The compound dose-dependently inhibited lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release in mouse primary peritoneal macrophages (MPMs). In addition, 7ae also exhibited promising in vivo anti-inflammatory effects in a LPS-induced mouse ALI model. To the best of our knowledge, this is the first “proof of concept” investigation on the potential application of a small molecule DDR1 inhibitor to treat ALI.",
keywords = "DDR1, acute lung injury (ALI), inflammation, inhibitor, structure−activity relationship (SAR)",
author = "Zhen Wang and Yali Zhang and Bartual, {Sergio G.} and Jinfeng Luo and Tingting Xu and Wenting Du and Qiuju Xun and Zhengchao Tu and Brekken, {Rolf A.} and Xiaomei Ren and Bullock, {Alex N.} and Guang Liang and Xiaoyun Lu and Ke Ding",
note = "Funding Information: The authors appreciate the financial support from National Natural Science Foundation of China (21572230 and 81425021), Guangdong Province (2013A022100038, 2015A030312014 and 2015A030306042, 2016A050502041), Guangzhou City (201508030036), and Jinan University. We also thank Diamond Light Source for beam time (proposal mx10619) as well as the staff of beamlines I04 and I04-1 for their assistance with crystal testing and data collection. The SGC is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, Canada Foundation for Innovation, Eshelman Institute for Innovation, Genome Canada, Innovative Medicines Initiative (EU/EFPIA) [ULTRA-DD grant no. 115766], Janssen, Merck and Co., Novartis Pharma AG, Ontario Ministry of Economic Development and Innovation, Pfizer, S{\~a}o Paulo Research Foundation-FAPESP, Takeda, and Wellcome Trust [106169/ZZ14/Z]. Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",
year = "2017",
month = mar,
day = "9",
doi = "10.1021/acsmedchemlett.6b00497",
language = "English (US)",
volume = "8",
pages = "327--332",
journal = "ACS Medicinal Chemistry Letters",
issn = "1948-5875",
publisher = "American Chemical Society",
number = "3",
}