title: Allosteric Inactivation of Polycomb Repressive Complex 2 (PRC2) by Inhibiting Its Adapter Protein: Embryonic Ectodomain Development (EED).
abstract: Aberrant PRC2 activity produces gene repressive epigenetic marks in multiple diseases and led to identification of Ezh2 as a drug target. Recent studies have shown that the epigenetic reader protein EED, associated with Ezh2 in PRC2, has an additional function to stimulate the PRC2 activity after binding to H3K27me3. Optimizing a compound known to block the H3K27me3 site in EED discovered by in-house screening, Novartis scientists have now produced a compound that shows durable tumor regression in a lymphoma xenograft model.
authors.affiliation: Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Chao-Yie
authors.identifier: 0000-0002-5445-0109
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Shaomeng
authors.identifier: 0000-0002-8782-6950
authors.initials: S
authors.lastname: Wang
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C491488:EED protein, human; D006657:Histones; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2