¹Department of Pharmacology, School of Medicine, University of California, Davis, Davis, CA, United States
²Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Türkiye
³Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Biruni University, Istanbul 34010, Türkiye
⁴Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956, Türkiye DOI : 10.29228/jrp.424 The Class III histone deacetylases protein Sirt2 has been implicated in the pathogenesis of several agerelated diseases such as inflammation, cancer, and type II diabetes and is considered an attractive novel therapeutic target. High-quality small-molecule inhibitors of Sirt2 are vital as chemical probes for target validation and potential starting points for new therapeutics. We applied an iterative virtual screening campaign including structure-based pharmacophore generation, ensemble docking, and protein-ligand interaction fingerprint analysis, to identify potential Sirt2 inhibitors from commercially available chemical libraries. Several hit molecules were determined to make exceptional interactions both with the catalytic (C) pocket and selective extended C pocket (EXC) pocket at the same time which indicated that these compounds represent promising lead structures for the development of selective and potent Sirt2 inhibitors. Keywords : Sirt2; virtual screening; pharmacophore; molecular docking; drug discovery