Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments

Giovanni Bottegoni, Marina Veronesi, Paola Bisignano, Puneet Kacker, Angelo D. Favia, Andrea Cavalli

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

In this study, we report on a virtual ligand screening protocol optimized to identify fragments endowed with activity at multiple targets. Thanks to this protocol, we were able to identify a fragment that displays activity in the low-micromolar range at both β-secretase 1 (BACE-1) and glycogen synthase kinase 3β (GSK-3β). These two structurally and physiologically unrelated enzymes likely contribute, through different pathways, to the onset of Alzheimer′s disease (AD). Therefore, their simultaneous inhibition holds great potential in exerting a profound effect on AD. In perspective, the strategy outlined herein can be adapted to other target combinations.

Original languageEnglish
Pages (from-to)1259-1263
Number of pages5
JournalChemMedChem
Volume11
Issue number12
Early online date10 Dec 2015
DOIs
Publication statusPublished - 20 Jun 2016

Keywords

  • BACE-1
  • GSK-3β
  • multitarget-directed ligands
  • polypharmacology
  • virtual screening

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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