Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry.
Novel bisaryl maleimide derivatives to mimic natural kinase inhibitors were prepared through click chemistry. A highly selective hit was discovered in a 124-kinase-assay, and docking studies revealed a π-π stacking interaction with the Phe67 at the P-loop of GSK-3β kinase.
College of Pharmacy and Tianjin Key Laboratory of Molecular Research, State, Nankai University, Tianjin, 300071, PR China.
Guoxian
G
Gu
Huihui
H
Wang
Pi
P
Liu
Chenzeng
C
Fu
Zhonghua
Z
Li
Xuefeng
X
Cao
Yunping
Y
Li
Qinghong
Q
Fang
Feng
F
Xu
Jie
J
Shen
Peng George
PG
Wang
D001665:Binding Sites; D057930:Click Chemistry; D003198:Computer Simulation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008301:Maleimides / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary
D008301:Maleimides; D047428:Protein Kinase Inhibitors; C043592:maleimide; D011494:Protein Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3