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

Research output: Contribution to journalArticlepeer-review

Authors

  • Marina Veronesi
  • Paola Bisignano
  • Puneet Kacker
  • Angelo D. Favia
  • Andrea Cavalli

Colleges, School and Institutes

External organisations

  • Istituto Italiano di Tecnologia
  • University of California, San Francisco
  • GVK Biosciences Pvt. Ltd.
  • Università di Bologna

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.

Details

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

Keywords

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