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https://www.arca.fiocruz.br/handle/icict/12712
HDAC8: A MULTIFACETED TARGET FOR THERAPEUTIC INTERVENTIONS.
HDAC8
Cornelia de Lange syndrome
cancer
schistosoma
X-ray crystallography
Author
Affilliation
Albert-Ludwigs-Universität Freiburg. Institute of Pharmaceutical Sciences. Freiburg, Germany
German Cancer Research Centre. Clinical Cooperation Unit Pediatric Oncology. Heidelberg, Germany
German Cancer Research Centre. Clinical Cooperation Unit Pediatric Oncology. Heidelberg, Germany/University Hospital Heidelberg. Department of Pediatric Oncology, Hematology and Immunology. Heidelberg, Germany
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Genômica e Biologia Computacional. Belo Horizonte, MG, Brazil
Martin-Luther-Universität Halle-Wittenberg. Institut für Pharmazie. Halle, Germany
Université de Strasbourg. Institut de Génétique et Biologie Moléculaire et Cellulaire. Département de Biologie Structurale Intégrative. Illkirch, France
Institut Pasteur de Lille. Université de Lille. Center for Infection and Immunity of Lille. Lille, France
Albert-Ludwigs-Universität Freiburg. Institute of Pharmaceutical Sciences. Freiburg, Germany
German Cancer Research Centre. Clinical Cooperation Unit Pediatric Oncology. Heidelberg, Germany
German Cancer Research Centre. Clinical Cooperation Unit Pediatric Oncology. Heidelberg, Germany/University Hospital Heidelberg. Department of Pediatric Oncology, Hematology and Immunology. Heidelberg, Germany
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Genômica e Biologia Computacional. Belo Horizonte, MG, Brazil
Martin-Luther-Universität Halle-Wittenberg. Institut für Pharmazie. Halle, Germany
Université de Strasbourg. Institut de Génétique et Biologie Moléculaire et Cellulaire. Département de Biologie Structurale Intégrative. Illkirch, France
Institut Pasteur de Lille. Université de Lille. Center for Infection and Immunity of Lille. Lille, France
Albert-Ludwigs-Universität Freiburg. Institute of Pharmaceutical Sciences. Freiburg, Germany
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.
Keywords
histone deacetylasesHDAC8
Cornelia de Lange syndrome
cancer
schistosoma
X-ray crystallography
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