Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a
Journal of Medicinal Chemistry2009Vol. 52(24), pp. 7950–7953
Citations Over TimeTop 10% of 2009 papers
Feng Liu, Xin Chen, Abdellah Allali‐Hassani, Amy Quinn, Gregory A. Wasney, Aiping Dong, Dalia Barsyte, I. Kozieradzki, Guillermo Senisterra, Irene Chau, Alena Siarheyeva, Dmitri Kireev, Ajit Jadhav, J. Martin Herold, Stephen V. Frye, C.H. Arrowsmith, Peter J. Brown, Anton Simeonov, Masoud Vedadi, Jian Jin
Abstract
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 remodeling.
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