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

@article{Liu2010ProteinLM,
  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},
  year={2010},
  volume={53 15},
  pages={
          5844-57
        }
}
  • 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
    151 Citations

    Topics from this paper

    Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines.
    • 90
    Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8
    • 49
    Structure-activity relationship studies of G9a-like protein (GLP) inhibitors.
    • 8
    Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase.
    • 27

    References

    SHOWING 1-10 OF 39 REFERENCES
    Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294
    • 231
    G9a and Glp Methylate Lysine 373 in the Tumor Suppressor p53*
    • 303
    • PDF
    A miniaturized screen for inhibitors of Jumonji histone demethylases.
    • 69
    DNA methyltransferase inhibitors and the development of epigenetic cancer therapies.
    • F. Lyko, R. Brown
    • Biology, Medicine
    • Journal of the National Cancer Institute
    • 2005
    • 445
    • PDF
    Targeting Methyl Lysine
    • 9