Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 11, Issue 3, Pages 379-384Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00495
Keywords
DDR1; selective inhibitor; NSCLC; drug discovery; SAR
Categories
Funding
- National Natural Science Foundation of China [81922062, 81874285, 81820108029]
- National Key Research and Development Program of China [218YFE0105800]
- Guangdong Province Science and Technology Program [2018A050506043]
- Jinan University
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DDR1 is considered as a promising target for cancer therapy, and selective inhibitors against DDR1 over other kinases may be considered as promising therapeutic agents. Herein, we have identified a series of 3'-(imidazo[1,2-alpha]pyrazin-3-yl)-[1,1'-biphenyl]-3-carboxamides as novel selective DDR1 inhibitors. Among these, compound 8v potently inhibited DDR1 with an IC50 of 23.8 nM, while it showed less inhibitory activity against DDR2 (IC50 = 1740 nM) and negligible activities against Bcr-Abl (IC50 > 10 mu M) and c-Kit (IC50 > 10 mu M). 8v also exhibited excellent selectivity in a KINOMEscan screening platform with 468 kinases. This compound dose-dependently suppressed NSCLC cell tumorigenicity, migration, and invasion. Collectively, these studies support its potential application for treatment of NSCLC.
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