3K5K

Discovery of a 2,4-Diamino-7-aminoalkoxy-quinazoline as a Potent Inhibitor of Histone Lysine Methyltransferase, G9a

Summary for 3K5K

• Entry DOI: 10.2210/pdb3k5k/pdb
• Descriptor: Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (7 entities in total)
• Functional Keywords: histone lysine methyltransferase, g9a, ank repeat, chromatin regulator, metal-binding, methyltransferase, nucleus, phosphoprotein, s-adenosyl-l-methionine, transferase, structural genomics, structural genomics consortium, sgc
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q96KQ7
• Total number of polymer chains: 2
• Total formula weight: 67615.08

Authors

Dong, A.,Wasney, G.A.,Liu, F.,Chen, X.,Allali-Hassani, A.,Senisterra, G.,Chau, I.,Bountra, C.,Weigelt, J.,Edwards, A.M.,Arrowsmith, C.H.,Frye, S.V.,Bochkarev, A.,Brown, P.J.,Jin, J.,Vedadi, M.,Structural Genomics Consortium (SGC) (deposition date: 2009-10-07, release date: 2009-11-10, Last modification date: 2024-11-20)

Primary citation

Liu, F.,Chen, X.,Allali-Hassani, A.,Quinn, A.M.,Wasney, G.A.,Dong, A.,Barsyte, D.,Kozieradzki, I.,Senisterra, G.,Chau, I.,Siarheyeva, A.,Kireev, D.B.,Jadhav, A.,Herold, J.M.,Frye, S.V.,Arrowsmith, C.H.,Brown, P.J.,Simeonov, A.,Vedadi, M.,Jin, J.
Discovery of a 2,4-diamino-7-aminoalkoxyquinazoline as a potent and selective inhibitor of histone lysine methyltransferase G9a.
J.Med.Chem., 52:7950-7953, 2009

PubMed 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.

PubMed: 19891491
DOI: 10.1021/jm901543m

Experimental method

X-RAY DIFFRACTION (1.7 Å)