7BTV
Crystal structure of EHMT2 SET domain in complex with compound 5.
7BTV の概要
エントリーDOI | 10.2210/pdb7btv/pdb |
分子名称 | Histone-lysine N-methyltransferase EHMT2, ZINC ION, S-ADENOSYLMETHIONINE, ... (5 entities in total) |
機能のキーワード | protein-small molecule inhibitor complex, transferase-transferase inhibitor complex, transferase |
由来する生物種 | Homo sapiens (Human) |
タンパク質・核酸の鎖数 | 2 |
化学式量合計 | 67272.95 |
構造登録者 | |
主引用文献 | Katayama, K.,Ishii, K.,Tsuda, E.,Yotsumoto, K.,Hiramoto, K.,Suzuki, M.,Yasumatsu, I.,Igarashi, W.,Torihata, M.,Ishiyama, T.,Katagiri, T. Discovery of novel histone lysine methyltransferase G9a/GLP (EHMT2/1) inhibitors: Design, synthesis, and structure-activity relationships of 2,4-diamino-6-methylpyrimidines. Bioorg.Med.Chem.Lett., 30:127475-127475, 2020 Cited by PubMed Abstract: The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors. PubMed: 32781218DOI: 10.1016/j.bmcl.2020.127475 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2 Å) |
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