title: Synthesis and biological evaluation of novel dasatinib analogues as potent DDR1 and DDR2 kinase inhibitors.
abstract: Novel dasatinib analogues as DDR1 and DDR2 inhibitors were designed and synthesized. The synthesized compounds were screened for DDR1 and DDR2 kinase inhibitory and cancer cell proliferation inhibitory activities. Some of the compounds showed the potent inhibitory activities against both DDR1 and DDR2, as well as anticancer activity in low nanomolar range against K562 cell line; especially, compound 3j demonstrated significantly better inhibitory potency than the parental dasatinib against both DDRs and also demonstrated the potent inhibitory activity against K562 cell lines (IC50values of 2.26±0.46 nm for DDR1, 7.04±2.90 nm for DDR2, and 0.125±0.017 nm for K562 cell line).
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|University of Chinese Academy of Sciences, Beijing, China.
authors: Lu
authors: L
authors: Liu
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|University of Chinese Academy of Sciences, Beijing, China.
authors: Muzammal
authors: M
authors: Hussain
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Jinfeng
authors: J
authors: Luo
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Anna
authors: A
authors: Duan
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Chaonan
authors: C
authors: Chen
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors: Zhengchao
authors: Z
authors: Tu
authors: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.|State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China.
authors: Jiancun
authors: J
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D000069439:Dasatinib / Q000031:analogs & derivatives* / Q000378:metabolism; D000070819:Discoidin Domain Receptor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000070820:Discoidin Domain Receptor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006860:Hydrogen Bonding; D020014:K562 Cells / Q000187:drug effects; D062105:Molecular Docking Simulation; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000077489:Piperazine; C092030:DDR1 protein, human; C000603239:DDR2 protein, human; D000070819:Discoidin Domain Receptor 1; D000070820:Discoidin Domain Receptor 2; D000069439:Dasatinib
keywords: DDR1; DDR2; anticancer activity; dasatinib; kinase inhibitor