In:
Molecular Informatics, Wiley, Vol. 40, No. 12 ( 2021-12)
Abstract:
Glycogen synthase kinase 3 beta (GSK‐3β) is considered as a promising drug target for the treatment of Alzheimer's disease (AD). In the present study, two compound libraries were selected for virtual screening based on pharmacophore models of GSK‐3β to discover new inhibitors. Nine potential hits were retained for biological investigation and four of these compounds showed GSK‐3β inhibitory activity (with the IC 50 values in sub‐micromolar range on GSK‐3β). Compounds 6 and 9 have good safety. They do not have any significant in vitro cytotoxicity against PC12 and SH‐SY5Y neuroblastoma cells at concentrations up to 90 μM. Based on the inhibitory activity and druggability properties, compound 8 is the preferred molecule, and it is a promising lead for the development of the GSK‐3β inhibitors for reducing the abnormal hyperphosphorylation of tau protein and relieving AD.
Type of Medium:
Online Resource
ISSN:
1868-1743
,
1868-1751
DOI:
10.1002/minf.202060031
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2537668-8
SSG:
15,3