title: Discovery and SAR of thiazolidine-2,4-dione analogues as insulin-like growth factor-1 receptor (IGF-1R) inhibitors via hierarchical virtual screening.
abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a growth factor receptor tyrosine kinase acting as a critical mediator of cell proliferation and survival. Novel 5-benzylidenethiazolidine-2,4-dione (5) and 5-(furan-2-ylmethylene)thiazolidine-2,4-dione (6) compounds were identified as potent and selective IGF-1R inhibitors via hierarchical virtual screening. Initial SAR and biological activity of the analogues of 5 and 6 with thiazolidine-2,4-dione template are presented, and several inhibitors with low nanomolar potency are reported.
authors.affiliation: Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Linjiang
authors.initials: L
authors.lastname: Tong
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
mesh_terms: D001667:Binding, Competitive; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D017526:Receptor, IGF Type 1