o:2885 Medicinal chemistry advances in targeting class I histone deacetylases en 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 1552099 10.37349/etat.2023.00166 2024-04-23T07:49:32.829Z 44 yes 46 Diaaeldin I. Abdallah University of Toronto Elvin D de Araujo University of Toronto person 0000-0003-0716-2830 Naman H. Patel University of Toronto person Lina S. Hasan University of Toronto person Richard Moriggl University of Veterinary Medicine Vienna person 0000-0003-0918-9463 Oliver H. Krämer University of Mainz person 0000-0003-3973-045X Patrick T. Gunning University of Toronto person 0000-0003-0654-735X application/pdf 2876657 https://phaidra.vetmeduni.ac.at/o:2885 no yes 16 70 1552253 Exploration of Targeted Anti-tumor Therapy 23 4 4 757 779 Open Exploration 2023