Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry

Guoxian Gu; Huihui Wang; Pi Liu; Chenzeng Fu; Zhonghua Li; Xuefeng Cao; Yunping Li; Qinghong Fang; Feng Xu; Jie Shen; Peng George Wang

doi:10.1039/c1cc15851a

Discovery and structural insight of a highly selective protein kinase inhibitor hit through click chemistry

Chem Commun (Camb). 2012 Mar 14;48(22):2788-90. doi: 10.1039/c1cc15851a. Epub 2012 Feb 8.

Authors

Guoxian Gu¹, Huihui Wang, Pi Liu, Chenzeng Fu, Zhonghua Li, Xuefeng Cao, Yunping Li, Qinghong Fang, Feng Xu, Jie Shen, Peng George Wang

Affiliation

¹ College of Pharmacy and Tianjin Key Laboratory of Molecular Research, State, Nankai University, Tianjin, 300071, PR China.

PMID: 22314408
DOI: 10.1039/c1cc15851a

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Click Chemistry*
Computer Simulation
Glycogen Synthase Kinase 3 / antagonists & inhibitors
Glycogen Synthase Kinase 3 / metabolism
Glycogen Synthase Kinase 3 beta
Maleimides / chemistry
Protein Kinase Inhibitors / chemistry*
Protein Kinases / chemistry*
Protein Kinases / metabolism
Protein Structure, Tertiary

Substances

Maleimides
Protein Kinase Inhibitors
maleimide
Protein Kinases
Glycogen Synthase Kinase 3 beta
Glycogen Synthase Kinase 3