title: Chemical probes targeting epigenetic proteins: Applications beyond oncology.
abstract: Epigenetic chemical probes are potent, cell-active, small molecule inhibitors or antagonists of specific domains in a protein; they have been indispensable for studying bromodomains and protein methyltransferases. The Structural Genomics Consortium (SGC), comprising scientists from academic and pharmaceutical laboratories, has generated most of the current epigenetic chemical probes. Moreover, the SGC has shared about 4 thousand aliquots of these probes, which have been used primarily for phenotypic profiling or to validate targets in cell lines or primary patient samples cultured in vitro. Epigenetic chemical probes have been critical tools in oncology research and have uncovered mechanistic insights into well-established targets, as well as identify new therapeutic starting points. Indeed, the literature primarily links epigenetic proteins to oncology, but applications in inflammation, viral, metabolic and neurodegenerative diseases are now being reported. We summarize the literature of these emerging applications and provide examples where existing probes might be used.
authors.affiliation: a Structural Genomics Consortium, University of Toronto , Toronto , ON , Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ackloo
authors.affiliation: a Structural Genomics Consortium, University of Toronto , Toronto , ON , Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brown
authors.affiliation: b Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences , Max-von-Laue-Straβe 15, Frankfurt am Main , Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Müller
mesh_terms: D000107:Acetylation; D057890:Epigenomics; D006657:Histones / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011496:Protein Methyltransferases / Q000737:chemistry / Q000235:genetics*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D006657:Histones; D054852:Small Molecule Libraries; D011496:Protein Methyltransferases; D008239:Lysine
keywords: Bromodomain; cardiovascular disease; histone arginine methyltransferase; histone lysine demethylase; histone lysine methyltransferase; inflammation; viral disease