title: Discovery of new Syk inhibitors through structure-based virtual screening.
abstract: Spleen tyrosine kinase (Syk) is an attractive target for the discovery of new treatments for inflammatory and autoimmune disorders. Structure-based virtual screening was performed for identifying novel scaffolds of Syk inhibitors. A total of 16 hits were discovered in the enzyme assay and 8 compounds had an IC50value lower than 10μM. In particular, compound 11 (IC50=3.2μM) was active in the cellular Syk assay and could inhibit lymphocytes proliferation in a dose-dependent manner, which could be used as a good starting point for the discovery of new class of Syk inhibitors.
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Naval Health Service and Medical Equipment, Faculty of Medicine, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: Youjun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Dong
authors.affiliation: International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: zhangwnk@hotmail.com.
authors.forename: Wannian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China. Electronic address: jianli@ecust.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: shengcq@hotmail.com.
authors.forename: Chunquan
authors.initials: C
authors.lastname: Sheng
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000072377:Syk Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000072377:Syk Kinase
keywords: Indazole-3-carboxamide inhibitor; Spleen tyrosine kinase; Virtual screening