6TEL
Crystal structure of Dot1L in complex with an inhibitor (compound 10).
Summary for 6TEL
| Entry DOI | 10.2210/pdb6tel/pdb |
| Related | 6TE6 |
| Descriptor | Histone-lysine N-methyltransferase, H3 lysine-79 specific, ~{N}1-[(~{S})-[2,2-bis(fluoranyl)-1,3-benzodioxol-4-yl]-(3-chloranylpyridin-2-yl)methyl]-~{N}2-(4-methoxy-6-piperazin-1-yl-1,3,5-triazin-2-yl)-4-methylsulfonyl-benzene-1,2-diamine, POTASSIUM ION, ... (4 entities in total) |
| Functional Keywords | dot1l, complex structure, inhibitor, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 78274.44 |
| Authors | Scheufler, C.,Stauffer, F.,Be, C.,Moebitz, H. (deposition date: 2019-11-12, release date: 2019-12-11, Last modification date: 2024-01-24) |
| Primary citation | Stauffer, F.,Weiss, A.,Scheufler, C.,Mobitz, H.,Ragot, C.,Beyer, K.S.,Calkins, K.,Guthy, D.,Kiffe, M.,Van Eerdenbrugh, B.,Tiedt, R.,Gaul, C. New Potent DOT1L Inhibitors forin VivoEvaluation in Mouse. Acs Med.Chem.Lett., 10:1655-1660, 2019 Cited by PubMed Abstract: In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local hypermethylation of H3K79 and consequently misexpression of leukemogenic genes. A structure-guided optimization of a HTS hit led to the discovery of DOT1L inhibitors with subnanomolar potency, allowing testing of the therapeutic principle of DOT1L inhibition in a preclinical mouse tumor xenograft model. Compounds displaying good exposure in mouse and nanomolar inhibition of target gene expression in cells were obtained and tested in vivo. PubMed: 31857842DOI: 10.1021/acsmedchemlett.9b00452 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.19 Å) |
Structure validation
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