Discovery of a 2,4-Diamino-7-aminoalkoxyquinazoline as a Potent and Selective Inhibitor of Histone Lysine Methyltransferase G9a
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- 作者：Feng Liu ; Xin Chen ; Abdellah Allali-Hassani ; Amy M. Quinn ; Gregory A. Wasney ; Aiping Dong ; Dalia Barsyte ; Ivona Kozieradzki ; Guillermo Senisterra ; Irene Chau ; Alena Siarheyeva ; Dmitri B. Kireev ; Ajit
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：December 24, 2009
- 年：2009
- 卷：52
- 期：24
- 页码：7950-7953
- 全文大小：789K
- 年卷期：v.52,no.24(December 24, 2009)
- ISSN：1520-4804
文摘
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.