title: HDAC8: a multifaceted target for therapeutic interventions.
abstract: Histone deacetylase 8 (HDAC8) is a class I histone deacetylase implicated as a therapeutic target in various diseases, including cancer, X-linked intellectual disability, and parasitic infections. It is a structurally well-characterized enzyme that also deacetylates nonhistone proteins. In cancer, HDAC8 is a major 'epigenetic player' that is linked to deregulated expression or interaction with transcription factors critical to tumorigenesis. In the parasite Schistosoma mansoni and in viral infections, HDAC8 is a novel target to subdue infection. The current challenge remains in the development of potent selective inhibitors that would specifically target HDAC8 with fewer adverse effects compared with pan-HDAC inhibitors. Here, we review HDAC8 as a drug target and discuss inhibitors with respect to their structural features and therapeutic interventions.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Alokta
authors.initials: A
authors.lastname: Chakrabarti
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Oehme
authors.affiliation: Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Centre (DKFZ), Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Witt
authors.affiliation: Genomics and Computational Biology Group, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
authors.affiliation: Institut für Pharmazie, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Département de Biologie Structurale Intégrative, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UDS), CNRS, INSERM, Illkirch, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Romier
authors.affiliation: Center for Infection and Immunity of Lille (CIIL), INSERM U1019 - CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany. Electronic address: manfred.jung@pharmazie.uni-freiburg.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: D000818:Animals; D003635:De Lange Syndrome / Q000188:drug therapy / Q000201:enzymology; D020536:Enzyme Activators / Q000737:chemistry / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011485:Protein Binding; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D012547:Schistosoma / Q000187:drug effects / Q000201:enzymology; D012552:Schistosomiasis / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases
keywords: Cornelia de Lange syndrome; HDAC8; X-ray crystallography; cancer; histone deacetylases; schistosoma