Pharmacophore-based Virtual Screening: Identification of Selective Sirtuin 2 Inhibitors


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Karaman Mayack B., Alayoubi M. M.

Journal of Research in Pharmacy, vol.27, no.4, pp.1366-1379, 2023 (ESCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 27 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.29228/jrp.424
  • Journal Name: Journal of Research in Pharmacy
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.1366-1379
  • Keywords: drug discovery, molecular docking, pharmacophore, Sirt2, virtual screening
  • Istanbul University Affiliated: Yes

Abstract

The Class III histone deacetylases protein Sirt2 has been implicated in the pathogenesis of several age-related 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.