title: Epigenetic drugs that do not target enzyme activity.
abstract: While the installation and removal of epigenetic post-translational modifications or ‘marks’ on both DNA and histone proteins are the tangible outcome of enzymatically catalyzed processes, the role of the epigenetic reader proteins looks, at first, less obvious. As they do not catalyze a chemical transformation or process as such, their role is not enzymatic. However, this does not preclude them from being potential targets for drug discovery as their function is clearly correlated to transcriptional activity and as a class of proteins, they appear to have binding sites of sufficient definition and size to be inhibited by small molecules. This suggests that this third class of epigenetic proteins that are involved in the interpretation of post-translational marks (as opposed to the creation or deletion of marks) may represent attractive targets for drug discovery efforts. This review mainly summarizes selected publications, patent literature and company disclosures on these non-enzymatic epigenetic reader proteins from 2009 to the present.
authors.affiliation: Pfizer Worldwide Research and Development, 200 Cambridgepark Drive, Cambridge, MA 02140, USA. Electronic address:dafydd.owen@pfizer.com.
authors.forename: Dafydd R
authors.initials: DR
authors.lastname: Owen
authors.affiliation: Pfizer Worldwide Research and Development, 200 Cambridgepark Drive, Cambridge, MA 02140, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Trzupek
mesh_terms: D000818:Animals; D001665:Binding Sites; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000378:metabolism*; D055808:Drug Discovery; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000235:genetics; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D006657:Histones; D054852:Small Molecule Libraries; D015254:DNA Modification Methylases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases