7DCF
Crystal structure of EHMT2 SET domain in complex with compound 10
Summary for 7DCF
| Entry DOI | 10.2210/pdb7dcf/pdb |
| Descriptor | Histone-lysine N-methyltransferase EHMT2, ZINC ION, S-ADENOSYLMETHIONINE, ... (5 entities in total) |
| Functional Keywords | protein-small molecule inhibitor complex, transferase-transferase inhibitor complex, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 67152.84 |
| Authors | Suzuki, M.,Katayama, K. (deposition date: 2020-10-26, release date: 2021-02-10, Last modification date: 2024-03-27) |
| Primary citation | Katayama, K.,Ishii, K.,Terashima, H.,Tsuda, E.,Suzuki, M.,Yotsumoto, K.,Hiramoto, K.,Yasumatsu, I.,Torihata, M.,Ishiyama, T.,Muto, T.,Katagiri, T. Discovery of DS79932728: A Potent, Orally Available G9a/GLP Inhibitor for Treating beta-Thalassemia and Sickle Cell Disease. Acs Med.Chem.Lett., 12:121-128, 2021 Cited by PubMed Abstract: Therapeutic reactivation of the γ-globin genes for fetal hemoglobin (HbF) production is an attractive strategy for treating β-thalassemia and sickle cell disease. It was reported that genetic knockdown of the histone lysine methyltransferase EHMT2/1 (G9a/GLP) is sufficient to induce HbF production. The aim of the present work was to acquire a G9a/GLP inhibitor that induces HbF production sufficiently. It was revealed that tetrahydroazepine has versatility as a side chain in various skeletons. We ultimately obtained a promising aminoindole derivative (DS79932728), a potent and orally bioavailable G9a/GLP inhibitor that was found to induce γ-globin production in a phlebotomized cynomolgus monkey model. This work could facilitate the development of effective new approaches for treating β-thalassemia and sickle cell disease. PubMed: 33488973DOI: 10.1021/acsmedchemlett.0c00572 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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