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A 2,6‐Disubstituted 4‐Anilinoquinazoline Derivative Facilitates Cardiomyogenesis of Embryonic Stem Cells
Author(s) -
Shen Guofang,
Hu Ying,
Wu Jianwei,
Jin Ke,
Zhu Danyan,
Zhang Yandong,
Yu Yongping,
Lou Yijia
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100603
Subject(s) - embryonic stem cell , chemistry , stem cell , quinazoline , microbiology and biotechnology , p19 cell , cell culture , biology , biochemistry , induced pluripotent stem cell , stereochemistry , genetics , gene
Abstract Chemical approaches are widely used in directed differentiation of embryonic stem (ES) cells. In our search for novel lead compounds that could facilitate cardiomyogenesis of ES cells, we designed a two‐step screening system based on P19 embryonic carcinoma and mouse ES cells. Application of this system to a quinazoline compound library including 2,3‐disubstituted 8‐arylamino‐3 H ‐imidazo[4,5‐ g ]quinazolines and 2,6‐disubstituted 4‐anilinoquinazoline led us to the discovery of compound 62 , which exhibits a stable cardiomyogenic effect on both P19 and mouse ES cells at a concentration of 0.1 μ M . An EGFR inhibition assay and molecular docking studies confirmed 62 as a potent EGFR inhibitor with a tyrosine kinase IC 50 value of 101 n M . However, major differences in cardiomyogenic activity were observed between iressa and 62 , indicating that other molecular events are also involved in compound 62 ‐induced cardiomyogenesis of ES cells.