Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.

@article{Liu2009DiscoveryOA,
  title={Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.},
  author={Feng Liu and Xin Chen and Abdellah Allali-Hassani and Amy M. Quinn and Gregory A. Wasney and Aiping Dong and Dalia Barsyte and Ivona Kozieradzki and Guillermo A. Senisterra and Irene Chau and Alena Siarheyeva and Dmitri B. Kireev and Ajit Jadhav and J. Martin Herold and Stephen V Frye and Cheryl H. Arrowsmith and Peter J. C. Brown and Anton Simeonov and Masoud Vedadi and Jian Jin},
  journal={Journal of medicinal chemistry},
  year={2009},
  volume={52 24},
  pages={7950-3}
}
SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template led to the discovery of 8 (UNC0224) as a potent and selective G9a inhibitor. A high resolution X-ray crystal structure of the G9a-8 complex, the first cocrystal structure of G9a with a small molecule inhibitor, was obtained. The cocrystal structure validated our binding hypothesis and will enable structure-based design of novel inhibitors. 8 is a useful tool for investigating the biology of G9a and its roles in chromatin… CONTINUE READING