title: Cellular analysis of the action of epigenetic drugs and probes.
abstract: Small molecule drugs and probes are important tools in drug discovery, pharmacology, and cell biology. This is of course also true for epigenetic inhibitors. Important examples for the use of established epigenetic inhibitors are the study of the mechanistic role of a certain target in a cellular setting or the modulation of a certain phenotype in an approach that aims toward therapeutic application. Alternatively, cellular testing may aim at the validation of a new epigenetic inhibitor in drug discovery approaches. Cellular and eventually animal models provide powerful tools for these different approaches but certain caveats have to be recognized and taken into account. This involves both the selectivity of the pharmacological tool as well as the specificity and the robustness of the cellular system. In this article, we present an overview of different methods that are used to profile and screen for epigenetic agents and comment on their limitations. We describe not only diverse successful case studies of screening approaches using different assay formats, but also some problematic cases, critically discussing selected applications of these systems.
authors.affiliation: a University of Freiburg, Institute for Pharmaceutical Sciences , Freiburg , Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hau
authors.affiliation: b Max Planck Institute of Immunobiology and Epigenetics , Freiburg , Germany.
authors.forename: Fides
authors.initials: F
authors.lastname: Zenk
authors.affiliation: c School of Pharmacy, University of East Anglia , Norwich NR4 7TJ , United Kingdom.|d Freiburg Institute of Advanced Studies (FRIAS), University of Freiburg , Freiburg , Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ganesan
authors.affiliation: b Max Planck Institute of Immunobiology and Epigenetics , Freiburg , Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Iovino
authors.affiliation: a University of Freiburg, Institute for Pharmaceutical Sciences , Freiburg , Germany.|d Freiburg Institute of Advanced Studies (FRIAS), University of Freiburg , Freiburg , Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: D019175:DNA Methylation / Q000187:drug effects*; D055808:Drug Discovery; D044127:Epigenesis, Genetic; D006801:Humans; D058990:Molecular Targeted Therapy; D054852:Small Molecule Libraries / Q000627:therapeutic use*
chemical_list: D054852:Small Molecule Libraries
keywords: Chem-seq; Chip-seq; Epigenetics; cellular models; chemical probes; epigenetic drugs; screening