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

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

  • J Med Chem. 2009 Dec 24;52(24):7950-3. doi: 10.1021/jm901543m.
Feng Liu 1,  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 Jadhav,  J Martin Herold,  Stephen V Frye,  Cheryl H Arrowsmith,  Peter J Brown,  Anton Simeonov,  Masoud Vedadi,  Jian Jin
Affiliations

Affiliation

  • 1 Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
PMID: 19891491 DOI: 10.1021/jm901543m
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.

Figures
Products