https://phaidra.vetmeduni.ac.at/o:2885 Medicinal chemistry advances in targeting class I histone deacetylases Abdallah, Diaaeldin I. Diaaeldin I. Abdallah University of Toronto Gunning, Patrick T. Patrick T. Gunning 0000-0003-0654-735X University of Toronto Krämer, Oliver H. Oliver H. Krämer 0000-0003-3973-045X University of Mainz Moriggl, Richard Richard Moriggl 0000-0003-0918-9463 University of Veterinary Medicine Vienna Hasan, Lina S. Lina S. Hasan University of Toronto de Araujo, Elvin D Elvin D de Araujo 0000-0003-0716-2830 University of Toronto Patel, Naman H. Naman H. Patel University of Toronto Open Exploration text eng Histone deacetylases (HDACs) are a class of zinc (Zn)-dependent metalloenzymes that are responsible for epigenetic modifications. HDACs are largely associated with histone proteins that regulate gene expression at the DNA level. This tight regulation is controlled by acetylation [via histone acetyl transferases (HATs)] and deacetylation (via HDACs) of histone and non-histone proteins that alter the coiling state of DNA, thus impacting gene expression as a downstream effect. For the last two decades, HDACs have been studied extensively and indicated in a range of diseases where HDAC dysregulation has been strongly correlated with disease emergence and progression-most prominently, cancer, neurodegenerative diseases, HIV, and inflammatory diseases. The involvement of HDACs as regulators in these biochemical pathways established them as an attractive therapeutic target. This review summarizes the drug development efforts exerted to create HDAC inhibitors (HDACis), specifically class I HDACs, with a focus on the medicinal chemistry, structural design, and pharmacology aspects of these inhibitors. cap group; epigenetic regulation; Histone deacetylases; medicinal chemistry; small-molecule inhibitors; zinc-binding group http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:2885/download 10.37349/etat.2023.00166 https://phaidra.vetmeduni.ac.at/o:605 application/pdf Exploration of Targeted Anti-tumor Therapy 4(4), 757-779 (2023) Exploration of Targeted Anti-tumor Therapy 4 4 757 779 2.74 MB 2023