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Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments
Author(s) -
Bottegoni Giovanni,
Veronesi Marina,
Bisignano Paola,
Kacker Puneet,
Favia Angelo D.,
Cavalli Andrea
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500521
Subject(s) - virtual screening , gsk 3 , computational biology , identification (biology) , protocol (science) , kinase , enzyme , chemistry , biology , biochemistry , drug discovery , medicine , botany , alternative medicine , pathology
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.