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 language | English |
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Pages (from-to) | 1259-1263 |
Number of pages | 5 |
Journal | ChemMedChem |
Volume | 11 |
Issue number | 12 |
Early online date | 10 Dec 2015 |
DOIs | |
Publication status | Published - 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