Discovery and SAR of thiazolidine-2,4-dione analogues as insulin-like growth factor-1 receptor (IGF-1R) inhibitors via hierarchical virtual screening.
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.
Liu
Xiaofeng
X
Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xie
Hua
H
Luo
Cheng
C
Tong
Linjiang
L
Wang
Yi
Y
Peng
Ting
T
Ding
Jian
J
Jiang
Hualiang
H
Li
Honglin
H
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*
D047428:Protein Kinase Inhibitors; D045162:Thiazolidinediones; C500090:thiazolidine-2,4-dione; D017526:Receptor, IGF Type 1