6YVI
EED in complex with a cyano-benzofuran
Summary for 6YVI
| Entry DOI | 10.2210/pdb6yvi/pdb |
| Descriptor | Polycomb protein EED, CALCIUM ION, N-(2,3-dihydro-1-benzofuran-4-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine, ... (5 entities in total) |
| Functional Keywords | methyl transferase eed prc2 epigenetic h3k27 wd40 inhibitor, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 85461.34 |
| Authors | Read, J.A. (deposition date: 2020-04-28, release date: 2021-05-12, Last modification date: 2024-01-24) |
| Primary citation | O' Donovan, D.H.,Gregson, C.,Packer, M.J.,Greenwood, R.,Pike, K.G.,Kawatkar, S.,Bloecher, A.,Robinson, J.,Read, J.,Code, E.,Hsu, J.H.,Shen, M.,Woods, H.,Barton, P.,Fillery, S.,Williamson, B.,Rawlins, P.B.,Bagal, S.K. Free energy perturbation in the design of EED ligands as inhibitors of polycomb repressive complex 2 (PRC2) methyltransferase. Bioorg.Med.Chem.Lett., 39:127904-127904, 2021 Cited by PubMed Abstract: Free Energy Perturbation (FEP) calculations can provide high-confidence predictions of the interaction strength between a ligand and its protein target. We sought to explore a series of triazolopyrimidines which bind to the EED subunit of the PRC2 complex as potential anticancer therapeutics, using FEP calculations to inform compound design. Combining FEP predictions with a late-stage functionalisation (LSF) inspired synthetic approach allowed us to rapidly evaluate structural modifications in a previously unexplored region of the EED binding site. This approach generated a series of novel triazolopyrimidine EED ligands with improved physicochemical properties and which inhibit PRC2 methyltransferase activity in a cancer-relevant G401 cell line. PubMed: 33684441DOI: 10.1016/j.bmcl.2021.127904 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
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