Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.

  title={Protein lysine methyltransferase G9a inhibitors: design, synthesis, and structure activity relationships of 2,4-diamino-7-aminoalkoxy-quinazolines.},
  author={F. Liu and X. Chen and Abdellah Allali-Hassani and A. Quinn and Tim J. Wigle and G. A. Wasney and A. Dong and G. Senisterra and Irene Chau and A. Siarheyeva and Jacqueline L. Norris and D. Kireev and Ajit Jadhav and J. Herold and W. Janzen and C. Arrowsmith and S. Frye and P. Brown and A. Simeonov and M. Vedadi and J. Jin},
  journal={Journal of medicinal chemistry},
  volume={53 15},
  • F. Liu, X. Chen, +18 authors J. Jin
  • Published 2010
  • Chemistry, Medicine
  • Journal of medicinal chemistry
  • Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. Genetic knockdown of G9a inhibits cancer cell growth, and the dimethylation of p53 K373 results in the inactivation of p53. Initial SAR exploration of the 2,4-diamino-6,7-dimethoxyquinazoline template represented by 3a (BIX01294), a selective small molecule inhibitor of G9a and GLP, led to the discovery of 10 (UNC0224) as a potent… CONTINUE READING
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